SRINAGAR: In a major breakthrough, a Kashmiri scientist along with a group of European scientists has discovered a new potential drug for the treatment of metastatic hypoxic cancers. The drug is currently in an advanced stage of further investigations post-animal trials.
Dr Musadir Nabi Peerzada (AIIMS)
Hailing from Muqami Shahwali in Kupwara’s Drugmulla belt, Dr Mudasir Nabi Peerzada led a team of eminent European scientists and co-workers to discover a new drug for the treatment of various metastatic hypoxic cancers.
Dr Peerzada who is currently working as a C-Level scientist at AIIMS New Delhi, has completed his postdoctoral training at the National Institute of Pathology. He was awarded a prestigious postdoctoral fellowship by the Indian Council of Medical Research (ICMR), Department of health research, Government of India.
The discovery is believed to help in silencing the HIF-1 factor-controlled human CAIX and CAXII activity in cancerous cells. The hCAIX and hCAXII are overexpressed in the renal, pancreatic, gut, oral, brain, lung, and ovarian cancers, therefore the drug could be significant in treating multiple cancers with greater efficacy.
Dr Mudasir said that he and his team strenuous efforts for many years to make this path-breaking discovery. The drug has shown satisfactory results in various tumour models and is currently undergoing advanced investigations.
“This discovery took us years of tests and trials. We tested it on animals before going ahead,” Dr Peerzada said, adding that the drug is undergoing advanced clinical trials for further investigation.
The study was published in ACS Medicinal Chemistry Letters entitled Discovery of Novel Hydroxyimine-Tethered Benzenesulfonamides as Potential Human Carbonic Anhydrase IX/XII Inhibitors was published on May 8, 2023.
He said that the new findings are remarkable in curing hypoxic cancers and will be a boon for cancer-related research.
The other scientists who are part of this invention include Dr Alessandro Bonardi, Dr Niccolò Paoletti, Dr Daniela Vullo, Dr Paola Gratteri, Dr Claudiu T Supuran, and Dr Amir Azam
Dr Peerzada is working on the development of anti-cancer therapeutics discovery taking into account the ATP binding site of kinases, hCAIX, hCAXII activity, cycle arrest at the G2/M phase of mitosis, prevention of HER2 dimerisation to deregulate PI3K/AKT and MAPK cell signalling pathways.
A young geneticist, Dr Rais A Gania was surprised to see his takeaways from his PhD were part of the text well before he entered the classroom as a teacher. Credited for identifying a particular enzyme that helps in crucial DNA copying, he is serving the IUST’s molecular medicine centre. In a freewheeling interview, he opens up about his research and future plans
TheNewsCaravan (KL): You studied in Kashmir and worked in different universities all over the world. How was your learning curve and what were the challenges you faced?
DR RAIS A GANAI (DRAG): I was born and brought up in the Posh-Kirri village of Anantnag. I did my primary schooling at Government Primary School in the same village. Later, I went to the Government Middle in the nearby Hugam village. Later, my father suggested me to complete further studies in Srinagar, as he was working at the University of Kashmir. Then, I went to the Starland High School Zakura and completed my matriculation there.
In Srinagar, I found it very difficult to compete with students because of the language barrier, as the medium of instruction was different. It was a challenging task to learn English and Urdu languages. It took me a lot of time to cope with the level of the students.
Then I completed my 10+2 from Soura Higher Secondary School. Afterwards, I went to the Islamia College of Science and Commerce, where from I completed my graduation. Even though there was not an ample structure at that time but the laboratories were well established. Attendance of labs was mandatory, due to which my scientific temper got developed.
After that, I was selected at the University of Kashmir for a couple of courses but I chose to study Biotechnology. After completing the Master’s degree in Biotechnology, I went to the Indian Institute of Science (IISc), Bangalore, where I worked under the mentorship of Prof Umesh Varshney and worked intensely on various Biotechnological challenges. He invested a lot of money, time and effort and taught me many new things due to which my interest in the research further deepened. During this time a few of my research papers were published.
Then I went to Sweden in 2009 for my PhD and completed it in 2015 and later got an international Postdoc fellowship offer in Sweden amounting to Rs 2.5 crore. I used that fellowship and immigrated to the USA. There I joined the NewYork based Howard Huges Medical Institute. I did research there for almost 2-3 years under the well-known researcher Danny Reinberg.
Then I came back to Kashmir as a Ramanujan Fellow. Initially, I joined the Central University of Kashmir and later moved to the IUST’s Watson-Crick Centre for Molecular Medicine in 2020.
KL: The work on genetics has been going on in all major universities throughout the world. However, we still have not understood the gene fully. What are the various challenges in understanding the gene, and what are the different goalposts we still have to reach?
DRAG: The gene is actually a small DNA sequence made of sugar bases like Adenine, Guanine, Thymine, and Cytosine (A, G, T, C). They are about 3 billion sugar bases called Nucleotides (made of Deoxyribose sugar, the Phosphate group, and the Nitrogen base) in a DNA molecule arranged in a chain structure. All the Nucleotides in a DNA molecule do not constitute genes, but only 1-2 per cent makes the genes and the rest 98-99 per cent of the base pairs do not attribute to the genes.
Scientists have identified most of the genes in our body and their functioning but the functioning of the rest 98 per cent of the non-genomic sequences (regulatory sequences) is still not known. We only know that these contain non-genomic sequences that regulate the genes, but the biggest challenge is to find out how 98 per cent of DNA regulates the 1 per cent of DNA.
The other major challenge was to understand the three-dimensional structure of DNA and its arrangement inside the cell. The chromosomes are arranged in compartmental structures. How and when these compartments are formed is yet to be discovered. How these genes are activated and repressed in the cells is still a challenge.
The actual structure of a DNA molecule has a three-dimensional chromatin architecture. These DNA molecules are present on the chromosomes. Our body contains 46 chromosomes in each cell that are intertwined inside the cell. The intertwined structure of chromosomes helps in the better expression of genes during cell division and cell formation. All the required genes express together and activate simultaneously in order to form a complete cell.
KL: What was your PhD all about and what were the major takeaways from your research?
DRAG: As I mentioned that DNA is a small molecule contained in a cell. A cell contains two meters of intertwined DNA, which if stretched is equivalent to at least four times the distance between the sun and the earth. During cell division and cell multiplication, this DNA is replicated/ duplicated which has to be very accurate. Genetic defects during cell division cause mutations/errors, which lead to genetic diseases, metabolic disorders, or even cancer.
During my PhD, my research was about the role of an enzyme called DNA polymerase in DNA replication. This enzyme reads, copies, and then makes the exact copy of a parent DNA molecule. The three billion nucleotides of a DNA molecule in a cell are copied accurately without any error or defect with the help of this enzyme. Besides, it also rectifies the errors, which are caused during cell division and helps in errorless duplication. Thus, the DNA polymerase enzyme not only plays a role in DNA replication but also fixes the errors caused during DNA replication, if any.
I also studied the functioning of various other enzymes but the pivotal research was about DNA polymerase. The majority of DNA polymerase enzymes look like, if I can say, a right-hand structure, containing a thumb, a palm, and fingers. The DNA polymerase, we studied has an additional domain called the P-domain, unlike the other DNA-Polymerase enzymes which only have three domains. The majority of DNA-Polymerase enzymes require a scaffold or support (called PCNA) for DNA copy and replication, but the DNA-polymerase we studied does not require PCNA rather it has the inbuilt P-domain that helps in DNA synthesis and thus does not require an outside scaffold. This was the biggest takeaway from my PhD research.
To my surprise, I later found when I was at the Central University of Kashmir, that our work and findings were published in textbooks, and are being taught to students in different Universities all over the world. It was a very difficult project to work on because nobody prior to us had worked on this. Our work was then published in the Journal Nature Structural and Molecular Biology, which now is a part of the textbooks and is being taught.
Dr Rais A Gania (WCCMM)
KL: What was your Post-doctorate research about, and what were your accomplishments and learnings during that period?
DRAG: I mostly studied two things during my Postdoc research, the role of epigenetic factors in the development, and the development of stem cells into the cardiomyocyte.
I actually wanted to expand and diversify my expertise, so I shifted to the field of epigenetics.
Under epigenetics, we study how the genes present in the DNA are regulated. Let us understand it this way – if we have two monozygotic twins and one of them is raised by the adopted parents and the other by the natural parents. Technically, after 30 years of age, both should be identical because of the principle of monozygotic nature, but because of the environmental effects, they would have developed variations over time. It is because the influence of environmental conditions affects the development of an individual and that regulates the body. Thus, the effect of an environment on the development over time, beyond the genetic basis and beyond DNA is called epigenetics.
There are thousands of genes on a DNA molecule and there are specific factors that actually regulate the functioning of these genes. I also worked on these factors.
DNA is wrapped around by the histone proteins. These proteins contain chemical modifications or tags that determine the function of the DNA sequence. I worked on early embryonic development, particularly on stem cells. I studied how differentiated development takes place from a single cell into different kinds of complex organs i.e., how a stem cell is transformed into a cardiomyocyte.
KL: How could you make lawmen understand this differentiation of a stem cell into different complex organs? What really controls this differentiation of cells? Is this also part of epigenetics?
DRAG: Nobody really knows how embryonic development occurs as it is not easy to study this field. People have now started research on it.
During embryonic development, the fusion of egg and sperm results in the formation of a Zygote, which later undergoes the 2-cell stage and the 4-cell stage, and so on. From day one of development certain genes are activated which stimulates the Zygote division and this division activates other genes, which then cause muscle cell formation. More and more genes get activated that guide the muscle cells to transform into different complex organs. It is mostly like this, but there is still ambiguity on how embryonic development takes place through different stages of development.
KL: What is your role at the IUST’s Watson-Crick Centre for Molecular Medicine and what are the different domains you are working on?
DRAG: I am establishing my lab here for research purposes. Besides, I am also the coordinator of the B Voc course on the Medical Lab and Molecular Diagnostic Technology. I teach students also. I guide students on how to do diagnostic tests and the process of opening diagnostic clinics.
The primary part of my job at the Watson-Crick Centre is to do research along with my students who work with me on the continuation of my PhD research work. We are studying the role of DNA polymerase enzyme other than the role of DNA synthesis.
Secondarily, we are also studying epigenetics. Epigenetic marks at different positions of a DNA molecule, other than the normal positions cause diseases like cancer, and developmental and neurodegenerative diseases, among others. Therefore, our aim is to research epigenetics in detail in order to develop drugs for the treatment of these diseases.
At NIT in Srinagar is a civil engineering professor who is passionate about machines. In the last few years, he has devised a basket full of interesting appliances and devices, with a focus on renewable energy and the people lacking access to better facilities for lack of power supply or resources, reports Masood Hussain
Prof Danish Ahmad (NIT Srinagar Innovator)
In the last 100 years, solar energy has emerged as a key player in managing humanity’s energy requirements. Now, solar energy is wheeled into power grids and sold with thermal and hydropower.
For off-grid areas and consumers lacking formal electricity supply set-up, however, solar energy is the only power source that they have access to. Most of the off-track underprivileged people use solar panels for lighting. There are a huge tribe of innovators and scientists who are working round the clock to make appliances that can give this population the luxury of using solar energy to have almost the same kind of life that exists elsewhere.
A NIT Product
One of these scientists is Danish Ahmad, a professor of civil engineering at Srinagar’s National Institute of Technology (NIT). Already acknowledged as the Best Innovator by the NIT for his commitment to developing innovations that serve underserved areas, he has spent years in innovating appliances that work on solar power. Passionate about using innovation to improve the lives of underprivileged classes living off the grid, he has devised a complete set of devices powered by solar energy.
What is interesting about Danish is that he did his BE from NIT and then a master’s from the same institution in water resources. Finally, as fate has it, he was appointed as a faculty in the same institution.
The First Innovation
Danish’s first invention was a modified, low-cost solar water purifier that utilises solar energy to purify dirty water through the process of evaporation and condensation. He has obtained the necessary patent and proprietary rights for this invention.
“When I devised it, somebody suggested me to patent the technology and I followed the process and in 2019, I got its patent,” Danish said. “It would find its use where there is no electricity and it is so efficient that you pour dirtiest water into it, it will use a cooling and evaporation mechanism to get you almost distilled water.”
Passion versus Profession
The senior faculty of the NIT, Danish said that his passion has led him to have a full-fledged workstation at home where he has been experimenting with device development. He teaches civil engineering but is passionate about mechanical engineering. “I was inquisitive from a very young age,” he said. “I would open any device and see how it functions and understand its mechanism.”
For the daytime, Danish teaches students at NIT. Back home he is working in his workshop, which is actually his laboratory. “It is a full-fledged workshop where most of these appliances were created,” Danish Ahmad said. “These are affordable solutions to situations that I released after watching the life of people living far away.”
Danish said he has almost 15 market-ready devices. My focus, he said is to have devices that have quick applicability and do not require the grid energy for use. His focus area has always remained the population that off track, off the grid.
Second Patent
Danish second patent came out of his tensions about how not to put off an LPG heater. Normally, he explained, when the LPG heaters are put on, these warm the room but generate a lot of smell as oxygen depletes and people have to switch it off and ventilate the room and resume the process.
Prof Danish Ahmad’s workshop at home led to as many as 18 innovations so far. KL Image
“I worked on a chimney that gets the gases out of the room but is sensitive enough to radiate the heat back,” Danish said. “A series of tests proved it to be efficient in retaining energy up to 85 per cent but still there is a loss of 10-15 per cent.” The technology fetched me a patent for a low-cost gas vent for LPG heaters.
His third project was the making of a solar water cooler for areas lacking electricity. “I used solar power as the energy base and create a cooler that would cool the liquid during the daytime on the solar energy,” Danish said. “In the night it starts consuming stored energy that it saves during the day operations. This fetches the facility a round-the-clock use.” This technology that adds a fan to the traditional system of cooling fetched Danish his third patent.
New Devices
In his career, Danish has been experimenting with many interesting ideas. He did succeed in devising many devices. Consumption of impure water, Danish asserts is key to disease. Water resources was been his subject during his studies, His focus remains on water.
Water filters are a twenty-first-century requirement but these are usually immovable devices and require energy for filtration. During travel, Danish said people usually lack knowledge about the source of pure water so in desperation they end up consuming impure water.
“With picnic-goers in mind, I devised a low-cost portable water filter. It is in fact a bottle filter,” Danish said. “Normally in energy-powered filters, it requires almost 30 minutes to get you cleaned water but the bottle I devised, it takes barely 30 seconds to one minute. Its rate of filtration is very high”.
Another of his devices is a portable instant water cooler. This device is aimed at offering an alternative to people who can either not afford a fridge or is travelling or on a picnic and wish to have cool water. His lunch-box-sized cooling system works on a car battery and has the capability of cooling water in 20 minutes.
Besides, he has invented a remote-controlled portable AC that also works on a car battery or small converters. “I have used a different technology in it which is completely different from the one used in fridges,” Danish said.
Out of curiosity, Danish said he invented a low-cost combination lock system that works on a 4-digit key. It has the possibility of changing the keys. “It was devised for people who have the habit of misplacing the key of formal lock systems,” Danish said. “It is cheap, durable and very simple.”
Another of his water-related devices is a solar-power water heater, which is portable. Again, aimed at people going to far-off places during hiking and travel who cannot have hot water for ablution and bathing. “It is foldable and within 15 minutes, it fetches water heated up to 60 degrees,” Danish said.
Survival Kits
What is interesting in Danish’s basket of inventions is the number of items that are devised for survival in trying situations.
One of the devices is an atmospheric water extractor that can draw water from the humidity in the air. “Consider a place where you do not have water at all,” Danish explains. “In such a situation, my device will help you suck water from the air. Its quantity will be small but, still, it will be enough to have water where there is no possibility of getting it otherwise.”
Danish is aware of the catastrophe that earthquakes wreck on earth and decimate societies. The tragedy is that earthquakes cannot be predicted. He devised a microwave sensory earthquake alarm system that works on sensitive technology. “It is established that people barely notice the first tremors that come before a major shock,” Danish said. “This device will alarm with every shock, regardless of the fact whether it is a small or a big tremor. Its alarm is so powerful that it will wake you up in the middle of your sleep and your neighbours too. It can help people get ready and stay cautious with the first tremor itself.”
In the earthquake warning system, however, the application for the patent has been filed by the NIT as an institution even though it is Danish who is behind the device.
Growing out himself, Danish has understood the challenges that senior citizens face. “Imagine a situation that the grandpa left for a morning walk with his walking stick in hand and a cell phone in his pocket and an hour left his phone is switched off because he had not charged the phone,” explains Danish. “I have devised the walking stick that has a phone charger in it. It will help him walk while his phone gets charged. It will help people, I believe.”
Other Devices
Most of the devices Danish has worked out are the outcome of the requirement. “We have Kangri as part of our culture but once you come from a day’s work, you do not have it ready at home,” explains Danish about an imaginary situation. “For such situations, I devised a portable energy-saving device that heats up within 15 minutes and requires a small energy that usually is consumed by a bulb. It can even be charged from a battery. It is much safer but obviously not an alternative to the Kangri that we must preserve.”
Besides, he has devised a robotic flower vase that is a novelty and works on sound control. It is aimed at replacing the plastic decorative flowers that people use and later throw away.
All these innovations are handy and portable and are aimed at the populations that live far away in uplands where natural water sources are scarce. Tens of thousands of people live uphill in the mountains of Jammu and Kashmir where supplying tap water is expensive and fraught with tensions, especially during winters. Besides, there are a lot of people who go up the mountains in herds for almost half of the year. These appliances are aimed at helping them have better life.
Market Ready Devices
Danish Ahmad said his innovations have received widespread recognition and praise from experts in the field. He has been invited to speak at numerous conferences and events, including once to a TedX Talk. His commitment to creating sustainable solutions for under-served communities has earned him a reputation as a leading innovator in the field of sustainable engineering.
However, what is interesting is that Danish’s innovations are yet to move from his laboratory to the market. Though he is open to the sharing of technology with the interested parties for mass manufacturing, there is some kind of disconnect that prevents people from using these appliances because they are yet to be manufactured at a mass scale.
“Learning is a lifelong process. You start it early and learn every day,” Danish said. “I am working on newer things while writing, devising and studying. I have done almost five courses online for which I had to sit in the examination even when I am myself a teacher.”
So far, Danish has filed 17 patents including the four – earthquake alarm system, floral vase, fruit harvester, and magnetic field detector – in which his employer institution is the applicant. “I have already three patents to my person and others are in the process of being granted,” Danish said. “After publication, it takes almost two years to get it granted formally but these all are published.”
While teaching and innovating newer things, Danish has not stopped writing. So far, he said, he has four books to his credit and some of them were translated into eight to ten languages for a wider audience. These include Solar Energy Utilization, Innovative Mindset, Water Quality Testing and Treatment and a book on innovations.
Right now, he is working on almost half a dozen other devices and some of them are close to a stage where he will be moving patent applications. Those ready and published include a fruit harvester that would prevent people from harvesting fruit without climbing the tree and a low-cost magnetic field detector.
“I am also waiting for the industry so that some of these technologies can be transferred for mass manufacturing. One thing you need to know is that I do not make prototypes, I make working products directly.”
A junior scientist at SKUAST-K, Dr Khalid Zaffar Masoodi is an award-winning biotechnologist who has been working on cancer biology. Founder of Kashmir’s first faculty-led biotech company of Kashmir, Cashmir Biotech Pvt. Ltd, he has been working on low-cost, healthy, non-toxic, and safe designer foods to cure and prevent various disorders including cancer through futuristic functional foods. Currently, his laboratory’s research is related to the identification of anticancer molecules for prostate cancer from medicinal plants endemic to Kashmir. In a freewheeling interview with Masood Hussain, he offers his knowledge about awareness to deliver and contribute new innovations in biotechnology and research on the causes, treatment and prevention of cancer through anticancer functional foods, designer foods, and superfoods.
TheNewsCaravan (KL): The conventional wisdom is that local issues have local solutions. Can we have local solutions to local health issues as well?
Khalid Z Masoodi (KZM): There are more than 200 types of cancer throughout the world and we can classify cancers according to where they start in the body, such as breast cancer ovarian cancer, prostate cancer, lung cancer etc. We can also group cancer according to the type of cell they start in and these cancers are increasing day by day worldwide. 20 per cent of these cancers are genetic in origin according to studies and 80 per cent are caused by environmental factors, food habits and lifestyle changes. These factors mutate the DNA and cause changes in normal cell growth.
For example, our bodies intake 210 mcg per day of cancer-causing hormone-disrupting chemical phthalates found in every soft and flexible plastic we use in our daily life. The beverages in the plastic bottle are injurious as these plastic containers have phthalates that bind to endocrine receptors and overexcite them resulting in malignancies.
In dark chocolates toxic metals are lurking, it is a state of serious concern as they cause cancer. Preservatives used in foods contain carcinogenic components. Every single person consumes 150 pounds or 60-88 kg of preservatives in a year. Most of the preservatives’ in vogue contain acrylamide which is carcinogenic. The most popular fast food of today’s generation is French fries, potato chips, pizza, and cold drinks in which the presence of Acrylamide and glycidamide has been found. Burgers contain Heterocyclic aromatic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Studies show HCAs and PAHs cause changes in DNA that may increase the risk of cancer. Pizza preservatives – TBHQ and BHA, has been identified as human carcinogen. 1n 2016 as we all know potassium bromate used to soften bread and in many other food items was banned in India as they were found carcinogenic during the course of research.
The estimated numbers of cancer in 2022 were 17 per cent in the case of breast cancer, 14 per cent in prostate cancer, 4.9 per cent in thyroid cancer, and lung cancer was estimated to be 14.3 per cent worldwide. Prostate cancer is the second leading cause of cancer-related deaths and the primary diagnosed cancer in men. No defined therapy against prostate cancer is present. Drugs cease to function after treatment in most cases. There is a need to cure and prevent deadly diseases with a healthier approach.
We define here the concept of Designer Foods that have added health benefits. Designer foods are normal foods fortified with health-promoting ingredients. These foods are similar in appearance to normal foods and are consumed regularly as a part of the diet. These foods are safe, non-toxic, organic, are cost-effective while the drugs available are cost-extensive and unaffordable by the majority classes of society and have added off-target effects.
We believe that a smart diet containing anticancer small molecules and molecules that can treat these disorders can help prevent these disorders The changing food habits of the modern world have changed, from green food (green vegetables), and herbs, to fast food, which is the main concern. We have experimentally shown that these greens, underutilised plants have high antioxidant properties. Some of our studies found some Haakh varieties have high anticancer potential against prostate and lung cancer cells.
KL: Can you tell us about your academic journey?
KZM: I completed my schooling at Burn Hall School, Srinagar and continued further studies at AMU. I completed my BSC (Hons) in Botany from AMU and pursued MSc and PhD in Plant Biotechnology from Jammu University under the mentorship of Prof Manoj K Dhar, former VC, University of Jammu, which I completed in 2010.
KL:What were the takeaways from your PhD?
KZM: During my PhD, I worked on the reconstruction of carotenoid biosynthetic pathway genes from purple-black carrot (Daucuscarota L). We successfully engineered E Coli that produced Lycopene and beta-carotene. Besides, we increased the production of these carotenoids using the Amplification Promoting Sequence, which increased the copy number of genes and hence their transcription and translation. We also worked on anthocyanins that act as effective natural food bio-colourant and real-time indicators of food spoilage that later helped in developing a smart gel that changes colour with a change in pH and can be used in food industries, biomedical industries and agriculture industries. Synthetic food colours pose a greater threat to humans and are responsible for causing various types of cancers and cardiovascular diseases.
KL: You continued your post-doctorate in the same field or we changed the subject?
KZM: The main expertise in cancer biology was gained during my post-doctoral associateship at the University of Pittsburgh, Pennsylvania, USA. There, I simultaneously worked on many projects related to gene and drug discoveries against prostate cancer.
We found the role of many genes in prostate cancer progression like ELL2, DHX15, PABPCA, EAF2, PRP8 etc. I also helped discover new androgen receptors targeting small molecules. I also increased the efficacy of IADT, the study which came out in the Journal of Urology, Journal of Endocrinology, Oncogene, Molecular Cancer Therapeutics, and PLoS One.
After my return from the USA, I worked as a Senior Resident at SKIMS, Soura for a short time before joining the Division of Plant Biotechnology, SKUAST-Kashmir as an Assistant Professor. The takeaway for me was that cancer cells are smart and if you try to target them through inhibition of the AR pathway they will salvage their survival through the PI3Kinase pathway. In metropolitan India, prostrate is now the third diagnosed cancer.
KL: You worked on cancer and then joined SKUAST-K which is all about agriculture. Is not it an interesting twist in the story?
KZM: It is always a challenge but biotechnologists revolve around the central dogma of molecular biology so DNA, RNA and proteins are the same which makes every organism. Upon my joining SKUAST-K, I surveyed various regions of Jammu and Kashmir to utilize the rich flora for new therapeutics against cancer.
It is very important that we do translational research that can result in an end product that can be commercialized and can be more useful than a mere publication or a patent. We knew that 60 per cent of the drugs in the market are plant-based or their analogues.
A rich repertoire of around 3054 medicinal and aromatic plant species (MAPs) are endogenous to Kashmir but were not explored for anticancer properties against prostate cancer through transcriptomics and AR targeted approach earlier. In a drug discovery programme initiated at SKUAST-K funded SERB, we screened 25,000 medicinal plant extracts from Kashmir’s around 350-400 medicinal plants. It resulted in the discovery of 16 new anticancer molecules against prostate cancer. Of these 16 molecules, five were from edible underutilised plants. Our laboratory has filed eight patents in the last three years.
Dr Khalid Zaffar Masoodi (SKUAST)
KL: Is there something that you can share with us about the new molecules you discovered?
KZM: The molecule SKIDDDL-1 present in the TaxO was the best among all the edible plants, which has been consumed for ages in Kashmir as a food supplement and as a vegetable. Over time, however, its use has diminished. This molecule effectively targeted androgen receptors in prostate cancer and decreased cellular progression, cancer cell migration (metastasis) in vitro and reduced tumour volume, and doubled the life expectancy in the mice xenograft model. A smart diet may help reduce the risk of developing prostate cancer, slow the progression of the disease, and prevent invasiveness and metastasis.
Awaiting a patent, we designed Magic Foods – a range of safe, non-toxic, plant-based anti-prostate cancer futuristic functional foods fortified with our secret TaxO that can be consumed on daily basis by populations worldwide that are at high risk of getting this peculiar cancer. The technology is cheap, safe and has no side effects.
Since SKUAST-K is the first Farm University to implement NEP 2020, now the faculty is permitted to have a start-up. I was joined by my two MSc students as directors of the faculty-led start-up. They are still studying but are job providers at the same time.
When we were doing this research, we had a great visitor from the University of Buffalo, Prof Samina Raja. We thought we can give something better to humanity if we worked together. So we have one collaborative project Haakh.
I am glad to share that soon you will have an anticancer Haakh variety. We are in the final stages of assessment and experimentation and after a thorough study of about 70 different variants of haakh we found some variants that have good activity against lung and prostate cancer.
The American University provided us with a small grant which we utilised in DNA bar-coding our Haakh, which can be accessed through GenBank. SERB, DST, Government of India has been kind enough and given me three successive grants without which what we did would not have been possible. My NC has always been my great support.
KL: Kashmir is India’s main apple basket. Have you worked on apple scab?
KZM: For Kashmir, agriculture is the backbone, especially the apple. The scab results in almost 30-40 per cent loss in apple. To prevent it we use around Rs 325 crore worth of fungicides which eventually go into our bodies through water and food. That is why people living around apple orchards have a higher incidence of endocrine-related issues.
We have worked on biotechnological approaches to scab pathogens in which we have identified new genes that can be used for producing cisgenic apples for scab resistance. This study was also published in one of the reputed high-impact journals. We used comparative transcriptome technology (RNA-Seq) for research that showed some genes expressed in the Maharaji apple and wild-type genotypes like Florina are not expressed in red delicious, so these genes can be transferred into red delicious to make the variety scab resistant. The process of producing cisgenic apples and breeding both techniques is underway.
KL:You have also identified some new wilt-causing pathogens. Tell us something about this.
KZM: One of my PhD scholars, Dr Tasmeen Parihar has identified six new Fusarium spp infecting solanaceous crops that were not earlier known to cause wilt in chilli, brinjal, tomato and capsicum. These findings came out recently in reputed journals.
We have many scientists in collaboration within and outside institutes. I am lucky to have good collaborations with Dr Zahoor A Bhat (Plant Pathology), Dr Khalid Bhat (Fruit Science), Dr Khursheed (Vegetable Sciences), Prof Mudasir Andrabi (Animal Biotechnology), Dr Tawheed Amin (FST) and many more.
KL: There is a major ethical debate regarding biotechnology, especially GM foods.
KZM: In biotechnology, we always have to face challenges related to transgenic plants but the fact is that in the near future (2050) breeding techniques will not be able to fulfil the need of the growing population. We will have to move towards biotechnology to feed the growing population of around 10 billion.
CRISP-Cas technology will enable us to knock out the antibiotic genes used in transgenic progress and we will have transgenic plants with only the gene of interest and not these antibiotic-resistant genes. Besides, we also use recombinant-based excision repair to make Cisgenic Apple. Since this research is going on we will have soon some good results.
After spending a lot of time trying to locate the particular molecules that play a role in diverse cancers, Dr Zahida Qamri changed her career path and started studying the quick response of societies to impactful science. She is currently working with JK Scientists where they handhold talent and guide the students in academics and research
TheNewsCaravan (KL): How you managed clinical trials during the Covid19 lockdown in the US?
DR ZAHIDA QAMRI (DZQ): In the Covid19 spread, the United States of America (USA) was taken off-guard. The healthcare system was not ready and we witnessed a healthcare crisis. The pandemic put the health systems under immense pressure and stretched them beyond their capacity. The disruption of the supply chain from China greatly affected the functioning of health institutions.
However, the experts successfully carried out vaccination trials in a considerably brief period of time. After clearing the phase-1 and phase-2 trials, the vaccine finally got FDA approval. Critically ill patients were given preference for receiving the vaccine dose. The government of the United States funded laboratories to get the vaccine ready in a minimum time span and the initial focus remained on genome sequencing. Researchers used to work day and night to find a single molecule, against which the vaccine could be produced. A Turkish couple finally succeeded in making the vaccine.
KL: What is your story from Kashmir to Ohio?
DZQ: My elementary education was completed at Netaji Memorial School in Balgarden. My high school years were spent at Caset Experimental School. Following that, I attended Kothibagh Higher Secondary School and then Women’s College on MA Road, where I earned my Bachelor’s degree. I then travelled to Delhi to further my education.
In the 1990s, moving to other states for studies was not an easy option in Kashmir, especially for women. But my family was very supportive towards my studies. Being the youngest among my siblings, I witnessed unparalleled encouragement. With the help of my siblings, I moved to Delhi, applied for the entrance test at Aligarh Muslim University and got into Jamia Hamdard. My initial years in Delhi didn’t go as I expected. It was a cultural shock, and added to it was the monsoon season. I had to stay at our principal RN Koul’s house for a year because I was unable to get hostel lodging. During that time, I had to commute between Faridabad to Delhi. So, it was quite challenging initially. However, with time I coped with the challenges and environment as well. I completed my master’s in Biochemistry. It was followed by a doctoral programme at Jamia Millia Islamia, New Delhi.
KL: What was your PhD thesis all about?
DZQ: In the Indian sub-continent, diarrhoea is one of the major health problems in children under one year of age. The diarrhoea-causing bacteria have various strains, among which few could turn out to be fatal. During my doctoral programme, I examined the stool of the children and developed DNA fingerprinting of the bacteria found. The purpose of my study was to identify and characterize the bacterial strains, which cause diarrhoea in infants. I also studied drug resistance among diarrhoea-causing bacteria.
KL: What were the major takeaways from your study?
DZQ: I discovered a small probe that could be used as identifying probe for bacterial strains and how to treat specific strains.
KL: Not all PhDs end up in discoveries. But there is a chain of follow-up studies. Has your PhD proven to be one?
DZQ: Yes, this topic was worked on under the guidance of my PhD supervisor until he retired. Much work has been done in this area in other parts of the world. In science, each investigation or study is an additional item to solve the puzzle and takes years to complete. Only then, can we get a clear picture of things.
KL: What did you do in your post-doctoral research?
DZQ: During my doctoral programme in microbiology, I developed an interest in oncology. I was selected in Safdarjung Hospital, New Delhi as a research scientist, where we worked on breast cancer. During our research, we hoped to identify a cancer-causing gene in the north Indian population. If we locate that gene in any person during genome sequencing, we can inform them about their propensity for cancer. It was during that time that there was a job opening at the Harvard Medical School for breast cancer. Since I had all the qualifications, I was called there. My first post-Doc was at Harvard Medical School.
Post Doc is basically a training that makes you think and analyse critically. It helps broaden our vision. As, I had studied breast cancer at Safdarjung Hospital, New Delhi, I incorporated brain and lung cancer in the study during my postdoc at Harvard. It was a great opportunity. I started drawing experiments and writing grants independently.
I spent 2.5 years at the Harvard Medical School. Then our lab was shifted to Ohio State University. I worked for 10-12 years as a postdoc there. However, due to a lack of funding, I was unable to get grants. So, I decided to get a master’s degree in Clinical and pre-clinical research from Ohio State University. The programme helped me to get into a new field of managing clinical research and locating the impact of the work in laboratories on common people.
Dr Zahida Qamri
KL: What is the status of cancer research? How long will cancer be a challenge to humanity?
DZQ: In this part of the world, cancer is seen as taboo. People suffering from cancer can’t reveal their condition to others because it is treated as an infectious disease. However, in western countries, a person mandatorily undergoes an annual check-up for cancer. So, if we are able to detect cancer at its early stage, we are able to cure the person. But the lack of pre-screening practice makes a large chunk of our population vulnerable to this deadly disease because the patient only comes to know about it when cancer overtakes his body. It is one of the reasons for the high mortality rates here. There is a need for awareness among the general population and to encourage them to go for annual check-ups. This can help us deal with the disease a little better.
KL: How relevant is the subject of clinical trials here? What are the new subfields of biochemistry that have better demand in the market?
DZQ: Clinical trials are a new and emerging discipline. For better management, Western countries are outsourcing the field. To enter the field, you do not require a specialist degree. Clinical trials are managed in a variety of cities in India, including Bangalore and Hyderabad. I am working with JK Scientists and we have conducted a few programmes on clinical studies and how our youngsters can look towards this area as their career. You may even participate from home. Internet access and electricity are two fundamental requirements in this field.
KL: A number of top professionals are serving major medical institutions across the world. Can there be some kind of outreach centre back home?
DZQ: Yes, of course, that is possible, but it requires infrastructure. The government must take the lead and provide the necessary infrastructure.
KL:Did you see any changes in Kashmir’s education system from the days when you were a student?
DZQ: Our youth are still confused about their education and employment. They do not have a long-term goal. I find it similar to what I witnessed 15-20 years ago. Our youth require suitable guidance on maintaining their attention on the good things.
Genome editing in livestock has the potential to bring about significant improvements in productivity, health, and welfare, but there are still challenges that need to be addressed.
A SKUAST-K scientist at work
The livestock industry is facing a growing demand for animal-based foods to feed the increasing human population. This forces a need for a more sustainable approach to livestock production that considers factors such as climate change, deforestation, and conservation of biodiversity, as well as ensuring animal health and welfare. The traditional approach to increasing livestock production has been to increase the amount of land used for feeding animals, but this no longer stands feasible due to limited space for grazing land on the planet.
The twenty-first century’s cutting-edge technologies, such as gene editing, can thus be harnessed to transform the livestock industry towards efficient and safe food animal production systems.
Genome editing technology is a set of tools that precisely modifies an organism’s genetic components. There are four major types of genome editing technologies used by molecular biology scientists: Mega nucleases, Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). All these technologies work by cutting the DNA at specific places which then triggers a repair mechanism. The repair process can either rejoin the broken ends of the DNA without the use of a template or with the help of a DNA template, which allows for the introduction of new sequences within the normal genes of the organism.
Amongst these four, CRISPR-based one is the most widely used genome editing tool due to its simplicity, efficiency, and low cost. However, the application of CRISPR-Cas9 technology in livestock (sheep, goat, cattle, and buffalo) requires advanced reproductive technologies for the delivery of editing components into reproductive cells or zygotes.
For effective gene editing, currently, the most common techniques are Somatic Cell Nuclear Transfer (SCNT) and zygote microinjection, but these methods are technically challenging, labour-intensive, and costly, limiting their use to only a few specialized laboratories.
Gene Editing
Genome editing technology has been applied in various areas of livestock production, including breeding disease-resistant animals, improving animal performance, altering milk composition, and producing hornless animals etc. Besides, CRISPR is often used for gene knockouts in medical research and therapeutic purposes. The traditional methods of livestock breeding have limitations, such as a long breeding cycle and a limited pool of genetic resources, making it difficult to improve livestock through conventional genetics. With genome editing technology, it is possible to make precise and heritable changes to the genome of diverse livestock species, leading to improved productivity, fertility, sustainability, and animal welfare.
To realise the full potential of genome editing technology in the livestock industry, it is necessary to develop strategies to translate established genome editing protocols into livestock breeding systems. The advanced reproductive technologies make it possible to apply genome editing on-farm, with minimal infrastructure and moderate cost. However, there is still a need for further research and development to ensure that the technology can be efficiently applied at scale. In conclusion, genome editing technology offers a powerful tool for improving the livestock industry, and its application has the potential to enhance productivity and profitability in livestock production.
Applications and Prospects
CRISPR is a cutting-edge gene editing technology that is rapidly gaining popularity in the livestock industry. Compared to traditional gene editings methods like ZFNs and TALENs, CRISPR is more precise and effective in modifying the genomes of livestock species. In the coming years, it is expected that CRISPR-based gene editing will be widely used in livestock breeding.
One of the primary applications of genome editing in livestock is to improve the productivity of livestock species. This can be achieved through the introduction of new traits, such as increased growth rate, improved feed conversion efficiency, and increased meat yield.
For example, researchers have used genome editing to introduce a growth hormone gene into chickens, resulting in birds that grow faster and produce more meat.
Similarly, genetic modifications have been made to pigs that improve the efficiency with which they convert feed into meat, resulting in higher meat yields per kilogram of feed. Knocking out the myostatin gene in cattle and sheep can lead to a double-muscling phenotype, resulting in superior meat production and this has been demonstrated by generating double-muscled mice who had their myostatin gene knocked out.
CRISPR can also be used to modify specific single nucleotide polymorphisms (SNPs) that impact economically important traits in livestock, such as reproductive performance. CRISPR can also be used to improve the nutritional content of milk produced by livestock. For example, knocking out the caprine beta-lactoglobulin gene in goats and introducing human lactoferrin (hlf) leads to reduced levels of beta-lactoglobulin in milk, and an increase in human lactoferrin.
CRISPR in livestock is being widely investigated for the creation of animals that are resistant to various diseases. For example, pigs that are resistant to Porcine Reproductive and Respiratory Syndrome (PRRS) can be produced by knocking out the scavenger receptor cysteine-rich receptor (CD163) gene. This leads to reduced economic costs and improved profitability of pig production, as well as reduced bio-security risks.
Cattle can also be made resistant to Mycobacterium bovis infection through genome editing, which causes significant economic losses and also poses a threat to human health. In cattle again genome editing has been used to develop cattle that are resistant to Bovine Spongiform Encephalopathy (BSE), a neurodegenerative disorder commonly referred to as mad cow disease. Likewise, CRISPR can be used to produce cattle that are resistant to Pasteurellosis, a respiratory disease caused by the bacterium Pasteurella hameolytica.
CRISPR-edited livestock are also relevant in biomedicine. For example, pigs can be edited to knock out certain genes, such as alpha-1, and 3-galactosyltransferase (GGTA1), to make them suitable for organ transplantation. Similarly, CRISPR can be used to generate livestock models for various human diseases, such as cardiovascular ailments, muscular dystrophy, and others. By knocking out the MHC system in pigs, CRISPR can also make them universal donors for organ xeno-transplantation.
Animal welfare is another important application of CRISPR in livestock breeding. Traditional methods of removing cattle horns can be painful and are not conducive to animal welfare. CRISPR-based gene editing offers a viable alternative by producing horn-free Holstein cattle.
Another application of genome editing in livestock is to improve their health, resistance to diseases and welfare. This can be achieved through the introduction of resistance genes, such as those that protect against specific viruses or bacteria, or through the elimination of genetic mutations that cause diseases. Animal welfare for example can be realized by genetic modifications to reduce the horns of cattle, reduce the need for painful dehorning procedures and reduce the risk of injury to both cattle and handlers.
Genome editing can also have a positive impact on the environment. By improving the efficiency with which livestock convert feed into meat, the demand for feed can be reduced, reducing the pressure on land used for crops and reducing greenhouse gas emissions from livestock.
Shortcomings
Regulation and Public Acceptance: The regulation and public acceptance of genome editing in livestock is still a challenge, as there are concerns about the safety and ethics of genetic modifications. There is resistance from consumers and regulatory bodies, and the regulatory environment for genome editing is still evolving, with different countries having different approaches to the technology.
Technical Challenges: The technical challenges associated with genome editing are another limitation, as the technology is still developing and has limitations in terms of precision and efficiency. The risk of unintended off-target effects and the difficulty of controlling the expression of edited genes are also challenges that need to be addressed.
Cost: The cost of genome editing is another limitation, as the technology is still relatively new and the cost of editing genes is high. The cost of commercializing genome-edited animals and bringing them to market is also high, which limits the ability of small farmers and start-ups to participate in this field.
‘We Are Nearly Successful In Creating Gene-edited, Cloned Embryos of High Yeilding Pashmina Goats’
Ethical Considerations: The ethical considerations associated with genome editing in livestock are also a challenge. There are concerns about the potential impact of edited genes on the environment and other species, as well as the potential for the creation of genetically modified organisms that could pose a threat to biodiversity.
While regulatory agencies may consider banning the production of such animals, this may be challenging to enforce due to the widespread availability of the technology. Instead of banning, it would be more effective to establish a registry of genome-edited livestock and monitor their reproduction and consumption through oversight mechanisms. This will help to identify any potential off-target mutations that may occur with the use of genome editing technology. Additionally, investment in public education to increase awareness of the risks and benefits of genome-edited livestock is crucial to ensure the responsible use of this technology.
In conclusion, genome editing in livestock has the potential to bring about significant improvements in productivity, health, and welfare, but there are still challenges that need to be addressed. The regulation and public acceptance of the technology, the technical difficulties associated with editing genes, the cost, and the ethical considerations are all those factors that need to be considered as the field of genome editing continues to develop.
(Prominent Kashmir scientist, Prof Riyaz A Shah is the Chief Scientist at Animal Cloning and Transgenic Laboratory, Division of Animal Biotechnology, Faculty of Veterinary Sciences SKUAST-Kashmir. To his credit is the first live cloned buffalo, the first ever animal cloned ever, in India.)
Working in SKUAST-K’s potato laboratory, a scholar was desperate for the MS media, a key ingredient for tissue culture but the lab lacked funds. It took her 28 months to discover a cheap alternative that is abundantly around the campus and it fetched her a prestigious grant to set up a unit for its production, reportsIfra Reshi
Sameena Lone, the young Kashmir scholar, who bagged a Rs 50 lakh grant from the respected BIRAC for her ground-breaking innovation, intends to change the way people look at the mounds of weeds that are perennially extracted from Dal Lake. She will be converting the weeds into a cheap medium for popularizing tissue culture.
A resident of Nishat Brein, Sameena, the daughter of a forest range officer, is a vegetable science scholar currently pursuing her PhD at SKAUST. She earned her bachelor’s and master’s in horticulture from SKAUST and her work on potato tissue culture started during her MSc. Working with her mentor, Dr Khursheed Hussain at the Potato Tissue Culture Laboratory, she recognized the high cost of nutrient media used in the cultivation of tissue cell culture.
“During the learning process, once we fell short of the Murashige and Skoog (MS) media that we were using in potato tissue culture, I posted my mentor. He said the laboratory can’t buy media for lack of funds,” Lone said while recalling the first time she felt the necessity for looking at the alternatives. “My mentor told me he was also looking for alternatives as he faced the same problem at his own end.”
It pushed the team on a hunt for an affordable, organic nutrient medium that would allow farmers to conduct tissue culture on their own, generating disease-free plantlets with lower pesticide loads.
After 28 months, “in a whistle-blow phenomenon, Coontail media came to the limelight”. After three years of research and standardization, she discovered that part of the weeds in Dal Lake are hugely nutrient-rich and can be used to create ideas for tissue culture. The success led her team to patent the idea and the associated processes. The idea was found to enable potato farmers to have affordable, organic potato tissue culture media, which not only reduces costs but also produces healthier, and disease-free potatoes.
This became one of its kind and the first Organic Tissue Culture Media to be used for the mass multiplication of high-quality, disease-free, and organic planting material of potato. Its success led Sameena to set up her own start-up, Kashmeer Organo Greens Private Limited with her mentor as co-founder. The unit currently operates from SKUAST-K’s Innovation, Incubation and Entrepreneurship (SKIIE) Centre.
= Having an idea and floating a start-up does not make a successful enterprise because it requires resources. Sameena’s Eureka moment in 2018, however, lacked an environment in which capital and resources could be even discussed. There was no concept start-ups, the way it is mainstream right now.
Things started changing fast as the team started talking about the idea. Almost in every competition of newer ideas, Sameena’s MS media was taken seriously.
The idea won the first prize in an Innovative Idea Presentation Competition organized by Maharaja Ranjit Singh College of Professional Sciences, Indore (MP), on the 36th National Science Day in 2022.
Back home, the idea got selected for seed funding from the JK Department of Science and Technology and IC.
Again, the idea also won first prize in Innovation Business Competition during the National Innovation Workshop held at Jammu on December 1, 2022, organized by GCET Jammu in association with IIT Kharagpur and the World Consortium of University held at Jammu.
Then came the final surprise when the idea, Organic and Disease-Free Seed Potato Production through Tissue Culture in Kashmir, bagged a prestigious grant from the Biotechnology Industry Research Assistance Council (BIRAC), a Not-for-Profit Company’ of the Government of India, which supports technology innovators and entrepreneurs to pursue a promising technology and establish and validate proof of concept (POC) for the idea under the BIG grant scheme. It is a Rs 50 lakh grant.
Sameena Lone, SKUAST-K PhD scholar, discovered a cheap alternative to MS media required in potato tissue culture. The media is being produced from locally available weeds, abundantly growing in Dal lake. The patented idea fetched her a Rs 50 grant to set up a start-up for producing tissue culture media. KL Image: Shuaib Wani
The grant is a very competitive one. More than 500 innovators had applied for the grant and only 26 were selected for the final pitching round before the panel. Eventually, only nine innovators were selected. “I was the only one from Jammu and Kashmir to receive the BIRAC BIG grant in the present round,” Sameena said.
“This has helped me realise my dream of doing something creative and something that was not done before,” a confidant Lone said. “Still, a lot of work is to be done.”
The grant is a staggered process that will release funds coinciding with the completion of the project within two years. There are key milestones in the implementation of the project, which are linked with the release of funds. The next step for this project includes product development at a commercial scale, demonstration trials, marketing at cost, and conducting awareness campaigns to educate people about the benefits of organic and healthy vegetables.
The unit is starting with four employees and the numbers will go up as per the demand. Anticipated to require almost four tons of weeds a year, the project will fetch Kashmir a reliable tuber for growing organic and disease-free potatoes. Estimates suggest, Kashmir grows 4500 tons of potato a year but the consumption is much more. Sameena’s innovation can help growers use the MS media and pick the tissue culture skill for better production at home.
Sameena and her scholar colleagues along with their mentors are working on developing anti-diabetic carrots in the SKUAST-Ks plant biotechnology department.
Kashmir neuroscientist, Dr Zahoor Shah, currently teaching at the University of Toledo, Ohio, is investigating the Gut-Brain axis in understanding various brain disorders, including Alzheimer’s disease. His research sees the gut as a major player in various diseases as the key organ is a universe of good and bad bacteria, he reveals in a detailed interview
TheNewsCaravan (KL): Is it true that most of the innovations and discoveries are logical explanations of conventional wisdom that humans already know?
DR ZAHOOR SHAH (DZS): Yes, You said it right. There is a role of human beings behind all the advancements in the world, even if you talk about artificial intelligence. All the inventions and technologies in the present world are because of human effort. Even if we talk about genetics, it was not taken into consideration in the past, but now it has changed science to a whole new level. For example, in the last ten years, there has been a tremendous amount of research on microbiota (bacteria in human intestines), which were not previously distinguished that much. Then, with time, scientists were able to discover their importance.
Overall, science has moved from conventional to new inventions. Scientists were able to discover new signalling pathways and causes of diseases in the body. There is a substantial increase in knowledge about medical science and a lot of enhancement in human health with technological advancements. Technology has helped us a lot. Now, we can isolate a minute gene from a cell and amplify it. We have also learned about the causes of diseases and found a cure that humans suffered through. Earlier, people would die young and nobody could explain why. Now we have progressed, and conditions can be identified earlier, and lives can be saved. It has led to longer life spans and a concept of slowing the ageing process and identifying causes that accelerates ageing and related diseases.
KL:How has your journey been till now and what were the struggles and milestones that you encountered from Srinagar to Ohio?
DZS: I did my schooling up to tenth standard at Shaheen Public School, and then twelfth from MP Higher Secondary School, Srinagar. I graduated with a BSc from SP College and worked part-time as a medical representative, where I became interested in drug discovery and development. That curiosity led me to pursue a Master’s degree in Toxicology at Hamdard University, Delhi. While pursuing my master’s, I got interested in research as I saw PhD scholars performing research in different areas of pharmacology and toxicology.
Fortunately, I got a chance to do my research on Neurobehavioral systems under famous neuro-behaviourist Dr SB Vohra, who is not unfortunately with us now. After finishing my PhD, I got an opportunity to do my first postdoctoral training with Dr David Gozal at the University of Louisville, Kentucky, for two and a half years. I studied sleep apnoea and identified biomarkers in the urine sample of children. The idea was to develop a diagnostic kit in which we could use a child’s urine sample to detect whether the child is suffering from sleep apnoea instead of a child going through excruciating overnight sleep studies. We identified a few biomarkers, and my mentor, David Gozal, patented the concept.
It is essential to mention that my PhD was on finding neuroprotective agents for ischemic brain injury. I was intrigued by the beneficial effects of natural plant products like green tea and Ginkgo biloba on human health. So I wanted to research whether these two natural products can help prevent stroke. Stroke is a leading cause of death and is caused by a clot that stops blood flow to the parts of the brain.
This was a game changer in my career as this concept helped me to receive a grant award when I moved to Johns Hopkins University for my second postdoctoral training. My mentor at Johns Hopkins, Dr Sylvain Dore, suggested writing a grant proposal on a novel natural product that could help in stroke prevention. Since I had already studied Ginkgo Biloba, I proposed the concept and received a highly competitive grant award from the National Institute of Health, Pathway to Independence. We fed Ginkgo biloba to animals and experimentally induced a stroke to examine whether it could show protective effects. After receiving the grant, I moved to the University of Toledo in 2009, where I got an independent position as Assistant Professor. There, I developed new research ideas as my interest grew in understanding the proteins or genes that are beneficial or harmful during a stroke. My team, including PhD students and postdocs, identified a protein crucial in stroke pathology. As the study progressed, we discovered its role in increasing inflammation in the brain in other conditions.
Here at the University of Toledo, I am in the Medicinal Chemistry Department and collaborated with a medicinal chemist. We synthesized a chemical molecule (drug molecule) against the gene we identified playing a crucial role in stroke pathology. We did preliminary studies using cell models of human haemorrhagic stroke and found the drug molecule is preventing neurons from the toxic effects of blood. Haemorrhagic stroke occurs when a brain blood vessel ruptures and causes bleeding. As a result, widespread neuro-inflammation ensues after the initial impact of bleeding. This is considered a debilitating disease, and around 50 per cent of patients remain immobilized for the rest of their lives.
Dr Zahoor Shah (University of Toledo, Ohio)
Since there is no drug available to treat haemorrhagic strokes, our idea was to make a drug molecule for reducing neuroinflammation. First, we developed a concept and sent the proposal to the National Institute of Health for funding. Fortunately, we received approximately US 2 million dollars for the research and development of the drug molecule. This research is ongoing, and we have received a US patent on this invention.
Our continuing efforts led my PhD students to research other conditions like age-related diseases and neuro-degenerative diseases that usually occur after the ’60s, such as Dementia, Parkinson’s disease, or Alzheimer’s disease. Most of these diseases have a single common component which is neuroinflammation. Therefore, we want to stop neuroinflammation so that old people become less prone to neurodegenerative diseases.
Besides, we also saw that neuroinflammation might have origins in other organs of the body. Certain diseases like Obesity, Diabetes, or Rheumatoid Arthritis have inflammation spread throughout the body. These inflammatory compounds do not enter the brain because the Blood Brain Barrier keeps harmful substances from entering the brain. But with age, this barrier also gets groggy and all the harmful inflammatory components cross into the brain resulting in neuroinflammation. This led to another intriguing question on gut microbiota and whether it has any role in neuroinflammation. Our intestines provide a conducive environment for essential bacteria that thrive on the fermentation of non-digestible fibres.
Conversely, people nowadays eat a lot of unhealthy Western food and fast food, which increases bad bacteria and decreases good bacteria in our gut, causing dysbiosis (an imbalance in the gut microbial community). Thus, we studied what effect gut dysbiosis will have on the brain, as it is well connected to the brain. For example, whenever we have to write an examination or make a presentation, we get nervous and anxious, which gives us a sense of butterflies in our stomach and results in a stomach ache or nausea. So, there is a bi-directional connection between our brain and gut. Therefore, we looked into what interchanges occur in the gut with ageing and its impact on our brain health.
For the last 12 years, I have been studying peripheral inflammation and now got interested to learn the microbiota-brain-axis in ageing. We performed experiments on aged mice and induced experimental inflammation to see whether it would change the microbiota. So, it came to be true and we observed an increase in the bad bacteria which caused the inflammation. We also observed markers of other neurodegenerative diseases in the brain. With this, we figured out that people with Diabetes, Rheumatoid arthritis, Obesity, Parkinson’s disease, and Alzheimer’s may have microbiota dysfunction. Along with this, we also observed female animals having higher Alzheimer’s Disease markers. Females are known to have a higher risk of Dementia related to Alzheimer’s disease than men.
We are currently working on the drug molecule, as I mentioned before and we are at an advanced stage of developing it.
KL: What were the different takeaways from your research and is there anything as such that is available and in practice on the ground level?
DZS: As I enunciated about my PhD research earlier, that was on Ginkgo Biloba. It is known to increase our memory. There have been many clinical trials in that aspect, but they didn’t prove successful. Patients above 70 years were recruited to see whether Ginkgo Biloba supplements would help enhance memory. I was at John Hopkins during this clinical trial, and our proposal of using a natural product for stroke prevention was fascinating and resulted in receiving the grant award. So, it was an outstanding achievement for me, as Gingko Biloba is already available in the market and has no side effects. If taken in minimal amounts has good health benefits. If at least 120 mg is taken daily, it can have good results and has no toxicity. This ground-breaking finding can benefit stroke prevention and help enhance memory in older people.
The other important achievement is the drug we are developing for neuroinflammation. I stated before the drug received the US patent and is ready to proceed in clinical trials and get FDA approval for clinical use.
KL:Subjecting to gut feeling or gut-brain axis, is it relevant to say that the brain has outsourced some of its functions to the gut?
DZS: That is an interesting question and an interesting idea to investigate. Our gut has major roles to play and is also considered a second brain because of its neural connections to the brain. The oesophagus and lining of the intestines to the rectum all have neural circuits that are controlled by the enteric nervous system (ENS), which is responsible for gastrointestinal behaviour. So, there is a bi-directional connection between the brain and the gut. Gut-brain-axis has many essential functions, including hormonal connections, and manage the immune system to some extent
For example, if we talk about Autism Spectrum Disorder (ASD), it has been found that the root cause is gut dysbiosis. Other disorders like Anxiety, Depression, or weight gain have also been seen to occur because of gut bacteria dysbiosis. There have also been experiments on weight gain in which faecal samples of overweight patients were taken and then implanted in mice. It was observed that the mice also gained weight due to bad microbiota. With that observation, it was observed that gut microbiota not only deals with gastrointestinal behaviour but also increases weight. So, it denotes that if we have a healthy gut, it can also control our weight. There are also a lot of clinical trials and research going on faecal implantation from healthy persons to patients with gut dysbiosis and syndromes like inflammatory bowel syndrome or irritable bowel syndrome.
KL: How sooner will we be able to see a shift in our routine toward something that is based on your path-breaking study?
DZS: For now, there has already been awareness, and people are moving towards a healthy lifestyle. The major takeaway is to take healthy foods that are rich in fibre. Usually, when we have fibrous food, it does not get digested in the upper colon but gets assimilated in the lower colon. After the assimilation, the material is left for the good bacteria to maintain equilibrium in the gut.
The drug molecule that I have invented may take time to come out. The least we can do now is change our unhealthy diet to a nutritious one, eat less red meat, and have more fibrous foods like green or leafy vegetables, onions, and garlic. We can also take supplements such as prebiotics and probiotics as well. Adding healthy habits in our daily life can help us keep our gut health, which will eventually positively impact our brain health.
KL:How true is the claim that if viruses and bacterial species will be eliminated from human existence, human survival won’t be the same?
DZS: That is true to reality. We have millions of bacteria and viruses in our bodies, which have a beneficial role to play. While alive or dead, bacteria are a very valuable assistance to our body. The good bacteria should not be eliminated and the bad ones must also be kept in check.
After death, the bacteria help decompose the corpse, and while living, it gives aid to our (GI Tract) gastrointestinal system. They release good products like short-chain fatty acids that help in weight loss and gut-related issues. It depends on us to manage the healthy bacteria in our bodies. They are a very important component of our lives.
Since 1997 when the first cloned mammal was born in Europe, there have been many abortive bids to use the technology in India. It was only in 2009, when Kashmir scientist, Dr Riyaz A Shah’s specially designed technique led to two cloned buffaloes in NDRI Karnal. Back home, after his PhD, he gave Kashmir the first cloned Pashmina goat, Noori, who is already a granny. In a detailed interview with Masood Hussain, Dr Riyaz explains his challenges and successes and his current research focus at SKUAST-K
TheNewsCaravan (KL): What is cloning and what are its applications?
DR RIYAZ AHMAD SHAH (DRAS): In normal conditions, animal breeding takes place by sexual reproduction, in which males and females physically get together to reproduce. However, cloning is an assisted reproductive technology, where the cells of either a male or female animal are taken and developed in laboratory conditions until an embryo is formed. It is then implanted in a surrogate mother. The offspring is born after it completes its gestation period. The process is efficient as it allows farmers to increase the number of their herds by providing more copies of the best-quality breed in the herd. In 1997, the world witnessed its first cloned mammal in the form of a sheep called Dolly, a female Finnish Dorset sheep cloned from an adult somatic cell
KL: Before we talk about your contributions to cloning, kindly tell us about your learning curve and the entire journey from your schools to SKUAST-K.
DRAS: I was born and raised in Batmaloo Srinagar. I did my early schooling at a local school and then joined Tyndale Biscoe for further studies. I aspired to be a doctor but couldn’t crack the entrance test; so, I ended up in veterinary science. I graduated from the Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST). Owing to a good number of vacancies in the field, I got a job immediately after completing my degree. However, the thirst for learning more and being mentored by professors who had completed their studies from other states inspired me to go for further studies outside Kashmir. I cracked the prestigious national veterinary entrance test and was post-graduated from Indian Veterinary Research Institute Bareilly, Uttar Pradesh.
I came back to Kashmir and worked in the Department of Animal Husbandry for some years. In 1998, I joined SKUAST as an Assistant Professor. Initially, I was posted at Cattle Farm in Manasbal, Ganderbal. It proved to be a good learning experience. In 2005, I got admission as an in-service PhD candidate at National Dairy Research Institute. There, I came across a group who were working on cloning at that time. Interested, I joined them. The group had been working on a project of cloning buffalo. The group was struggling to form a cloned embryo since 1997 but could not succeed. I took the challenge and my PhD guide Dr S K Singla encouraged me for it. It took me nearly two years to standardize various techniques related to cloning but I succeeded.
KL: What were the major takeaways of your PhD programme?
DRAS: The topic of my research was the production of handmade cloned embryos in buffalos. The embryo formed in the laboratory was transferred to a surrogate mother. It was sheer luck that I got the best quality cloned embryos. After completing the gestation period, a healthy buffalo was born on February 6, 2009, at National Dairy Research Institute (NDRI), Karnal. It was named Samrupa, the world’s first cloned buffalo calf. It made headlines throughout the world. I did not anticipate such a positive outcome. The calf, however, succumbed to lung infection a few days after it was born.
It was followed by another healthy and normal cloned calf named Garima, born on June 6, 2009.
KL: How many scientists were successful in the process of cloning development before you?
DRAS: My guide, Dr SK Singla, already had his PhD in clone generation under his credit but he remained unsuccessful in the formation of a live and healthy cloned progeny. During the course of my research, two other students were working on the same topic. However, they failed to get any positive results. Samrupa was the first live birth of a cloned buffalo at the institute and proved to be a milestone. Since then the institute has produced 20-25 cloned buffalos. The process involved in Samrupa and Garima acted as a road map for the researchers, who are now merging it with the science of gene editing to incorporate the selective qualities in the cloned organisms.
KL: When you were back home, you cloned Noori, the first Pashmina goat in March 2012?
DRAS: After I finished my PhD and returned to SKUAST, we started working on the Pashmina goat clone. We had to first set up facilities here at the SKUAST campus in Shuhama because we lacked the infrastructure. With project funding of Rs 2.50 crore from the Indian Council for Research (ICR), we were able to acquire basic equipment for our research.
Our objective was to develop a cloned embryo, implant it into a female and get a viable cloned organism. Noori was one of the clones. While earlier researchers had tried to develop clones of various species but Pashmina goat was never experimented on. So, we had to start from scratch. We isolated and cultured the cells of the Pashmina goat. We conducted a study on the different species that can provide oocytes. We had to employ the Pashmina goat’s somatic cells and an egg from a different species.
Since people do not prefer goat meat in Kashmir, we had to get access to the ovaries of goats from a slaughterhouse in Delhi. This made the process a bit hectic and it took us two years to standardize the techniques. However, we got successful in the development of cloned embryos, which were then implanted into a surrogate mother. After 20-25 unsuccessful trials, Noori was our first live cloned Pashmina goat. Noori is currently living a normal and healthy life. It has given birth to 5-6 offspring via the natural reproductive process. Noori has also been a source of Pashmina wool like other naturally produced Pashmina goats.
Dr Riyaz A Shah (SKUAST-K)
KL: What are the differences between naturally reproduced organisms and cloned ones?
DRAS: A clone is genetically as good as a naturally bred organism. Cloning allows choosing the characters and traits we want in an organism, thus allowing farmers to increase the overall quality of their breed. Cloning also enables the production of the desired gender of a species. Farmers for example prefer a cow over a bull, cloning helps them have as many cows as they desire.
KL: How different is Noori from her mother and her own offspring?
DRAS: Noori’s mother was a naturally bred Pashmina goat. Its embryo was implanted in a surrogate mother, who also happened to have naturally reproduced. After Noori’s birth, we studied its physiology and other parameters and found it and its progeny as good as any other Pashmina goat. We concluded that it can be used for the same purposes as we do use a normal goat. Also, there is no restriction on it or its progeny being used as food.
KL: What has been your research focus since you completed the landmark Noori’s project?
DRAS: After Noori’s success, we approached various institutes for funding our projects. We got successful and secured a project, where we introduced gene editing in cloning. We tried to incorporate CRISPR-Cas9, a naturally occurring genome editing system in our research. We identified the gene responsible for Pashmina production in Noori and now we are trying to edit the gene so that the cloned progeny will be a source of good quality and improved quantity of Pashmina. We are nearly successful in creating gene-edited and cloned embryos. We are hopeful that we will soon be able to witness its progeny as well.
Simultaneously we are working on gene editing in sheep, where our focus is to increase meat production. This is a collaborative project with ICR, while scientists outside with the same objective are working on buffaloes; we are at the same time working on sheep.
KL: What ethical issues do genetically modified organisms (GMOs) face?
DRAS: One of the main ethical issues that GMOs face is their uncontrolled use. Many countries have allowed using GMOs as food. But yes scientists first have to make sure that gene editing does not lead to any abnormality in the organism.
A teacher, researcher and innovator, Dr Jameel A Khan’s expertise in developing drought-tolerant varieties has helped address climate change challenges. Currently serving as Programme Manager at C-CAMP, one of the respected addresses for cutting-edge research and innovation, the young scientist reveals his learning curve and the contributions he made to the agricultural science
TheNewsCaravan (KL):What are the new goals in agricultural sciences for increasing production?
DR JAMEEL A KHAN (JAK): During the green revolution of the 1960s, there was a growing demand for increased food production due to a rapidly growing population. MS Swaminathan employed genetics knowledge to meet this demand and address the issue of food scarcity. One of the strategies employed was to cultivate short-stature crop varieties instead of tall ones, as the tall ones had a tendency to fall over, causing crop loss. This strategy successfully addressed the issue of lodging and increased food production. As the population continues to grow, biotechnology will become a key area of intervention in agriculture, aimed at meeting the demands of the next green revolution.
KL:So what is the status right now?
JAK: While current agricultural yields are stable, there are still major challenges such as droughts, pests and diseases, and post-harvest losses. Improving storage technologies and addressing these issues will help meet the food needs of both current and future populations. Approximately 40-50 per cent of food production is lost due to factors such as drought, heat, salinity, and floods. To address these issues, biotechnology has a significant role to play in finding solutions for these challenges and reducing post-harvest losses.
KL:Before we go into your accomplishments and research can you offer us details about your learning curves and challenges faced during your career journey?
JAK: I started my educational journey at New Convent, Gogji Bagh, Srinagar where my teachers instilled in me the importance of thinking big and pursuing my dreams. After completing the 10th standard, I decided to study BSc in Agriculture at SKUAST, Jammu. I then went on to secure a seat for a Master’s in Plant Biotechnology at the University of Agricultural Sciences, Bangalore by qualifying for the national level exam JNU-DBT. Initially, I had intended to follow in my brother’s (Er. Muneer Khan) footsteps and pursue a career in engineering, as he had studied at SSM. However, I decided to forge my own path when I went to a counselling session and ended up being selected for BSc Agriculture, my parents were astonished but happy.
Eventually, I did a PhD in the same field. I was the sole individual from Kashmir to secure a PhD in UAS-Bangalore at that time.
I was determined to do something innovative in my research and this led to the start of my journey in innovation. Throughout my academic journey, I faced challenges but my determination and hard work helped me secure my place in the field of Plant Biotechnology.
KL:What were the key takeaways from your PhD?
JAK: Research can be as brief as a one-page publication, as evidenced by Watson and Crick’s research on the structure and model of DNA, which won a Noble Prize. This just goes to show that the length of scientific research can range from being short to extensive, like discussions on black holes. The human genome, which can be measured in megabytes and terabytes, contains vast amounts of information that we are now able to comprehend. Similarly, research on genes related to human traits such as appearance (eye colour and height) and behaviour (intelligence, addiction, and even depression) etc., are influenced by gene expression. Researchers are understanding which genes are responsible for these traits. For example, if I wanted to select intelligence, I would look for someone with genes that express high intelligence.
In the realm of plant research, we divide the phenotype into visual and performance aspects, as we observe how plants perform under biotic and abiotic stress, such as water scarcity in agriculture, particularly in rice cultivation. It takes about 2500 litres of water to produce one kilogram of rice, from growth to consumption. By reducing water consumption in rice cultivation by just 10-20 per cent, we could make a significant impact on humanity. Rice can now be grown without stagnant water in a field, thanks to the research I have been a part of.
During my PhD, I worked on exploring the phenotypic and genotypic factors affecting plant growth and productivity, specifically focusing on rice cultivation. I developed a technology for root phenotyping and utilized German technology at the ICAR-National Institute of Abiotic Stress Management. This was a major milestone as it was the first platform of its kind developed in India and I made it available to other scientists by not patenting it. My aim was to make advanced technology accessible to farmers at an affordable cost.
My research also involved studying the genes that express high levels of root growth and analysing the correlation between gene expression and phenotype. By combining both phenotypic and genotypic information, I was able to gain a better understanding of the factors affecting plant growth and productivity.
I also looked at the impact of abiotic stress, such as water scarcity, on agriculture and specifically rice cultivation. I found that a significant amount of water is required for rice growth and that reducing water consumption by just 20-25 per cent can lead to a big step towards sustainable agriculture. Our laboratory developed a rice variety called aerobic rice that utilizes deep roots to absorb water from deep soil, thereby saving 20-25 per cent of water compared to traditional rice varieties.
Overall, my PhD research aimed to improve our understanding of the factors affecting plant growth and productivity and to develop practical solutions to reduce water usage in agriculture.
KL:Is this rice variety being grown anywhere?
JAK: At present, the government of Katakana has already approved the growing of this rice cultivation. Our technology is ready for any future water scarcity and is proven to be effective. We have taken a thorough approach to this technology, even down to the genetic level, to ensure that farmers can access the aerobic rice variety ARB6 (BI 33) whenever they may need it in the future.
KL:Does aerobic rice BI 33 require specific ecology for growing?
JAK: ICAR has a policy of multi-location trials, which must be completed before any new variety of rice can be approved. Recently, Tamil Nadu scientists conducted research on drought-resistant varieties, with BI 33 outperforming all other varieties in the trials. This variety has now been approved, after having passed all tests.
KL:How does it work on a yield?
JAK: Despite a 5% drop in yield, the comparison between aerobic rice and rice grown in water is not applicable here. We are instead comparing how rice will be grown using technology in the future when water scarcity becomes more severe.
KL:Will this technology ever suit growing rice in Kashmir?
JAK: Kashmiri people rely heavily on rice as their main source of food, and the agricultural sector is always looking ahead to anticipate potential needs and address potential issues. In the case of a water scarcity crisis in Kashmir, science and technology are prepared to mitigate any potential losses in yield. Scientists are always looking forward, anticipating the needs of the future, and this is what drives the research and development of new technologies–even if it may seem out of reach at the present moment. For instance, Elon Musk’s ambitious plans to take humans to Mars or the Moon demonstrate the potential for future technology to make the seemingly impossible a reality. In this way, my own work falls in line with this outlook, searching for solutions that may open up new possibilities.
Dr Jameel A Khan (Agriculture)
KL:With immense success in your field of research, why you changed your career path?
JAK: I have always been passionate about technology and its potential to innovate and create a bigger, brighter future. With a background in agriculture, I wanted to be part of the Agrotechnology revolution that is currently taking place in India. My experience has enabled me to understand how technology can be used in the most effective ways, and I am eager to use my knowledge to contribute to the industry.
Also, the recent initiatives in Agritech and the focus on agriculture accelerators in the budget proposed by the Government of India indicate that research must be effectively adapted and implemented for real-world applications. This emphasis on agriculture accelerators in the budget is a clear sign that the government is actively pursuing work that can have tangible impacts on the agricultural sector, which could have a significant ripple effect throughout the country. We at C-CAMP have been forefront runners in such research and innovations.
KL:What are the present projects you are working on?
JAK: At the Centre for Cellular and Molecular Platforms (C-CAMP) in Bangalore, we are part of the Bangalore Life Science Cluster (BLiSC) and have three major institutions and top bio incubators. C-CAMP has been awarded the best incubator of India across all sectors, owing to our expertise in life sciences, be it biotechnology, agro technology, health technology, or any other industrial biotechnology. We also received an award during National Startup Day as the best Ecosystem Enabler in India. We feel proud to contribute to bioeconomy in India. We provide the handholding for the latest technologies that a startup or an individual innovator is working on.
I handle multiple programs, the basic objective is to assess the proposal, considering its scientific acumen, financial theme, and future innovation in technology. We provide a grant of Rs 50 lakhs for eighteen months to help develop a product and mentor the startup with proper guidance for early-stage innovators.
I work on a programme where we train innovators to find a relevant problem and make a venture out of it. In this programme along with a monthly fellowship of Rs 50,000, a kick-start grant is given. Young innovators in Kashmir should consider applying for this programme.
At C-CAMP, I also work with the Centre of Excellence in Agriculture with the objective to identify gaps in agriculture. We were successful in handholding startups that are making a national impact, for example, Krishitantra.
KL:What are the innovations taking place in agriculture? Is there any contribution from Jammu and Kashmir in Agrotechnology?
JAK: Agriculture is undergoing a transformation due to the introduction of innovative technologies. Indoor vertical farming is one of the most popular advancements, as it increases crop yields and reduces the negative impact on the environment. Farm automation technology is also becoming increasingly popular, as it automates the crop or livestock production cycle. In addition, livestock technology is being used to monitor health and increase productivity through wearable sensors. Other innovations that are expected to hit the market include agricultural robotics, artificial intelligence in agriculture, and the use of drones. All of these technologies are helping to make agricultural processes more efficient and effective.
The Vice Chancellor of SKAUST-K has been a great mentor to me and has taken a number of new and innovative initiatives at the university. In Kashmir, it can be difficult to get acceptance for new ideas and advancements, but many universities like SKUAST have taken steps to bring about change. I also met the VC of Kashmir University and the DIQA Director, I could see the enthusiasm to work on innovations.
There are many innovators who have applied for these projects, and I have taken on the role of mentor, as I feel that it gives me a chance to give back to the community. We also have the JK Scientist programme, which helps students to get accepted for doctorates and PhDs.
I take this platform for productive collaboration with C-CAMP for making impactful innovations in life sciences.
