The Awantipora Molecule

Merely moving ahead of the embryonic stage, the IUST’s Watson-Crick Centre for Molecular Medicine (WCCMM) is expected to be a major address for research in sunrise science. Manned by a young and ambitious trio with fair experience in the world’s best laboratories, the centre has the potential of offering answers to some key crucial questions in the coming days, reports Masood Hussain

Scientists and scholars of the IUST’s Watson-Crick Centre for Molecular Medicine (WCCMM). KL Image: Bilal Bahadur

For encouraging science to get some space in hugely politicised and almost-stagnant Kashmir campuses, the efforts of two academic administrators would require acknowledgement – Prof Talat Ahmad and Dr Mushtaq Sidiqui, the former Vice Chancellors of the University of Kashmir (KU) and Islamic University of Science and Technology (IUST). They found enough space in the already established government initiatives to create two scientific research centres – the Centre for Interdisciplinary Research and Innovation (CIRI) and Watson-Crick Centre for Molecular Medicine (WCCMM), in 2019 and 2020, respectively.

The follow-up was swift and professional. Dr Shakil A Ramshoo, the Dean of Sciences at the University of Kashmir, contributed to the proper establishment of the CIRI. Soon, he was appointed the VC of the IUST where he is literally on tenterhooks to make WCCMM a world-class centre for scientific research. What contributes to his fast decision-making is his background – he is an earth science scientist, who has contributed to helping Kashmir understand the fast changes taking place between the tree line and the snow line.

Though the brain-gain-focused fellowships are a Government of India baby, Ramshoo is personally involved. “IUST genuinely wants to excel rather than just muddle along, thus we are looking for the brightest minds with a variety of scientific talents and viewpoints as well as the abilities of all types of minds,” Ramshoo recently put a note on his Facebook page. “We are seeking highly qualified, imaginative, self-driven, and passionate scientists to lead the labs and show a creative, multidisciplinary approach to any area of science and technology. People of any gender, caste, creed, race, or colour who can provide these qualities are welcome at IUST.”

Ramshoo’s Rise

The Bejbehara-born, Ramshoo studied Forest Hydrology and Watershed Management in Jharkhand and did his masters in Space Technology from the Asian Institute of Technology in Thailand. He later moved to the University of Tokyo for his PhD in Water Resource Engineering and worked for four years at the Japan Aerospace Exploration Agency (JAXA). Since 2004, he has been in Kashmir.

His research at the PhD level revolved around the “use of remote sensing for developing hydrological, vegetation and climate change applications”. He actually used Scholarly articles for Polarimetric (PolSAR) interferometric (InSAR) for assessing the soil moisture under varied field conditions. Back home, he used remote sensing and Geographic Information System (GIS) to explore and analyze 15000 glaciers in Kashmir in the backdrop of the valley emerging as the crucible for climatic change. “On the basis of my contribution in the cryosphere studies, I received a grant to Rs 20 crore to study the impact of climate change on western Himalayan glaciers,” Ramshoo said. “In 2009, I successfully established India’s first National Ice-core Lab at the University of Kashmir.”

His year-in-year assessment has led to the calculation that if things do not change, Kashmir will lose almost 70 per cent of the glaciers by the end of this century. “The average temperature increase of Jammu and Kashmir is way more than the projected average rise in the global and national temperatures by the end of the century,” Ramshoo regretted. “Against the global increase of 0.8 degree Celsius, Jammu and Kashmir has recorded an average 1.3 degree Celsius rise in temperature which is very alarming.” Tragically the crisis lacks any contributions from Kashmir. “The western disturbances originating in the Mediterranean traverse through most industrialized regions of the world including Europe and carry a large amount of greenhouse gases before hitting our region.”

Understanding the requirements for doing impactful science has made Ramshoo literally a crusader for the cause. He knows how the lack of adequate infrastructure and livelihood issues have pushed the best brains from Kashmir to serve in remote well-established research centres. That is why he is keen to get the best within the brain-gain and re-entry schemes that various Government of India initiatives envisage. He knows the loopholes too.

“When these scientists come back to India for research, they face a lot of uncertainty because they avail the fellowship for few years only,” Ramshoo said. “After completing their fellowships here, they don’t have an option but to go back.” So they devised a way out by offering the best minds that they will be adjusted as Associate Professors soon after they complete the five-year fellowship. That addresses the uncertainty to a larger extent but it eventually will depend on how many positions, a university will have to offer.

How this pans out in near future is too early to predict. The fact is that it has started the process of science being taken seriously in the campuses. The WCCMM, now located in the 2-storey building has already published “more than 10 research publications” in 2021, with an average impact factor of 11.0. Gradually the faculty at the WCCMM is improving. Almost every member has a roller-coaster ride in pursuit of science.

A Promising Team Leader

A young and promising molecular biologist, Dr Muzaffar Ahmad Macha heads the IUST’s ambitious science project. Basically from Tral, not far away from the campus, Macha has crossed oceans in pursuit of science and his contributions are being referred to in the scientific community. After graduating from SP College, he moved to Jamia Hamdard and earned his master’s as one of the toppers. This helped him join as a researcher at AIIMS’s biochemistry department for almost six years for his PhD before he moved to Omaha (USA) based University of Nebraska Medical Centre (UNMC) for his post-doctorate, a campus where he later taught and supervised research in head and neck surgery. Back home as Ramanujan Fellow in 2020, he spent quite a few months at the Central University of Kashmir before choosing the newly established WCCMM as his research base.

“It was the family situation and my desperation to return home and contribute to the science that brought me back,” Muzaffar said. “I applied for both fellowships and got both.”

“My primary research focus in the last 15 years of research career has been on the molecular mechanism of deregulated signalling, Tumour microenvironment, chemo and radiation sensitivity and Development of Genetically Engineered Mouse Models (GEMMs) for Head and Neck and Oesophageal Cancer pathogenesis,” Dr Muzaffar said. “Currently I am working on developing novel models for Oesophageal Cancer, the highly prevalent cancer in Jammu and Kashmir. We are in collaboration with experts in Artificial Intelligence at IUST to develop unique tools for guiding precision medicine to cancer patients.” Jammu and Kashmir has the third highest incidence of oesophageal cancer after China and Japan.

Explaining his core focus, Muzaffar said that cigarette smoking and Gutka (smokeless tobacco) consumption are the main reasons for very high incidences of head and neck Squamous Cell Carcinoma (HNSCC) in India. At AIIMS, Macha said he worked on the “identification of novel signalling pathways which are being affected by the smoking use”. Besides, he “identified several natural compounds, which inhibited these signalling pathways and could be used for prevention of the development of HNSCCs”.

In his post-doctoral research at the University of Nebraska Medical Centre, Muzaffar identified the very important role of a glycoprotein “MUC4” in the development of these cancers. “During my tenure as an Assistant Professor at UNMC, I along with my Postdoctoral fellow worked on the role of a transcription factor on HNSCC and pancreatic cancer,” Muzaffar said. “In this study, we identified a novel mechanism of this protein in the process of perineural invasion (a unique phenomenon of cancer cells to metastasis through neurons) and development of pain in cancer patients.”

Muzaffar continues to retain the thread and focus of his lifelong research. “We are currently trying to identify novel inhibitors of this protein that may inhibit not only the progression of cancers but may also inhibit metastasis and subside pain in cancer patients. We also are working on the development of novel in vitro models to understand the underlying biology of some very high incidence cancers in Jammu and Kashmir.”

A Roller Coaster Ride

Molecular biologist, Dr Rais A Ganai has also an interesting and impressive story. Hailing from Posh Kreri village near Bejbehara, his knowledge of the English language was restricted to 26 letters till his eighth class. He studied at government schools which were usually referred to be Urdu-medium schools but were actually restricted to his mother tongue. Basic English would make a sort of guest appearance in the syllabus in sixth class and then it would get complicated with every new class in such a way that lot many students would give up studies altogether.

“When my father took me to Srinagar, all of a sudden, I felt as if I landed in a different world, where I could neither communicate in Urdu nor I could properly understand the English,” Rais said. “It took me more than two years to address the language deficit but somehow I managed it.”

For his 10+2, Rais was enrolled in the state-run Higher Secondary School in Soura and later at the Islamia College of Science for his bachelor’s. Rais is all praise for the Islamia College where the teachers ensured the students attend laboratory and get the best in the given situation. “The college then was operating from huts as the main buildings were destroyed but the laboratories were functioning properly,” Rais remembers. “The teachers were strict and uncompromising.”

After getting his master’s in Biotechnology from the University of Kashmir, Rais moved to the Department of Microbiology and Cell Biology at the Indian Institute of Science in Bangaluru as a researcher. Soon, his application for PhD was accepted at the Umea University in Sweden. “Because of my work during my PhD, I bagged the best fellowship from Swedish Research Council as my application was rated outstanding,” Rais said about his PhD that fetched him Rs 2.5 crore of funds for post-doctorate. While this fellowship enabled him to fly to New York University’s Howard Hughes Medical Institute for a post-doctorate for three years, another Rs 80 lakh fellowship by the Swedish Medical Society for Medical Research gave him an opportunity to work in the US for two more years. His DST-SERB Ramanujan Fellowship fetched him Rs 1.10 crore grant to work at WCCMM.

Rais was briefly at the Central University of Kashmir. It was there that got a surprise. In the textbooks, he was teaching, he found the mention of a discovery to which he had contributed as a researcher. “It is amazing that sometimes what you try to teach is something that you helped discover,” Rais said.

“I was fascinated by the flawless transmission of genetic material in the form of DNA, from one generation to the next to preserve the information it contains. Any errors during this process would otherwise lead to the loss of information or the development of diseases,” Rais said while talking about choosing the particular stream for his research. “I worked on one of the key proteins involved in the synthesis of DNA called DNA polymerase epsilon. The development of colorectal cancer has been linked to mutations in this protein, making it a prime target for therapeutic interventions. We studied the mechanisms by which it synthesized DNA with high accuracy. We discovered that this protein has a unique domain not present in any other protein in a cell. We named that domain as “P” domain. This domain imparts high proofreading and processivity to this protein, which promotes error-free DNA synthesis.”

In his post-doctoral research at Howard Hughes Medical Institute, Dr Rais decided to study how epigenetics played a part in the formation of various tissues in our body.

Epigenetics is described as factors controlling life beyond the usual heredity DNA sequences. Much as how remote controllers would adjust the function of the DNA and genes within it. It helps these genes to either turn “on” or “off” and one of the ways it does is through chemical modifications of DNA.

“I studied how these chemical modifications affect the formation of heart cells during early embryonic development using embryonic stem cells,” Dr Rais said. “We discovered how certain chemical modifications are important for the development of one cell type but not the other. These studies will eventually have an impact on stem cell therapy, which uses lab-grown cells to repair damaged tissue in a patient.”

Currently, Rais’s scholars are studying both these areas. “We are trying to understand how these processes can go wrong in a cell leading to the development of various diseases including cancers,” Dr Rais said.

The Prostate Cancer

From the Saffron lands of Pampore, the WCCMM has Dr Arsheed A Gania, a trained biochemist who specialises in creating biomarkers for certain diseases. Schooled locally, Arsheed did his senior secondary at Iqbal Memorial School and later joined SP College and finally landed in KU’s biotechnology department for a master’s.

“Those were the days when I was confused about the future course in my life,” Arsheed said. “I did not know whether I should study further or I should prepare myself for the KAS.” During his masters, he used to visit IIM-Jammu for a six-month training course that opened a window of interest for him. There, he got a person who motivated him to go for research and not any other occupation.

“After getting JRF, I moved to Institute of Microbial Technology Chandigarh (CSIR-IMTECH) and did my PhD under Dr Charu Sharma and then I went to Masonic Cancer Centre, at the University of Minnesota in the US where I did my post-doctoral research,” Arsheed said. “I was an Assistant professor for three years before moving to the WCCMM in 2020 summer.”

At PhD level, Arsheed worked around Tuberculosis, especially trying to find the pathway of interaction between the mycobacterium and the human body trying to find out which protein of the bacteria has the capacity to hijack the host cell’s immune system and destroy it. “It was all about the host-pathogen interaction of mycobacterium tuberculosis, particularly the role of Rv3810 and RV2418 in the Pathighogenesis of TB,” Arsheed said.

In post-doctoral research, however, his focus remained on cancer; especially pancreatic and prostate cancer which has a high incidence in the US. He bagged President’s Fellowship which fetched him US$ 60,000, a year to study cancer. “I was trying to understand the role of genetic and epigenetic pathways to prostate and pancreatic cancer,” Arsheed said.

It was Arsheed’s expertise in prostate cancer research that enabled him to write an impressive application that paved his way to return home. “Unlike the US where three lakh people report prostrate and 35000 of them die in a year, the disease witnessed a huge jump in India, especially in the metropolitan cities in last thirty years,” Arsheed said. “My question was to find out why it happened and why in Kashmir, unlike other cancers, prostate cancer has a low incidence. Is it because the crisis is not reported or simply there are other issues.” He hopes some ideas on this will be very visible once the pilot studies – currently in progress, will be out within two years. His laboratory is also attempted to create certain biomarkers for Neuroendocrine prostate cancer (NEPC), an aggressive variant of prostate cancer, the pathology of which has remained a challenge to the scientific community, so far. “We are working on drug resistance and next-generation immunotherapy in neuroendocrine cancers.”

An Immunologist Dean

The IUST has managed a senior hand to oversee the science on the campus. Dr M Ayub Qadri has remained with the National Institute of Immunology since the days when it operated from a few rooms at the AIIMS, Delhi. Studying in different schools in Srinagar city, Ayub disliked the idea of getting into medicine or agriculture. After his master’s in Chemistry, he, for the first time decided to move out of Kashmir, an idea that shocked his parents because he had never moved an inch beyond Jammu.

“At RRL Jammu (now IIIM-CSIR), he got fascinated by a paper that talked about the discovery of Monoclonal antibodies,” Qadri remembers. “With the master’s in chemistry in hand, one day, he moved out and within a few days visited TATA Institute of Fundamental Research in Mumbai, another research centre at Hyderabad and finally decided to work at the NII in AIIMS. “It was a huge jump from chemistry to biology and finally to immunology.”

After his PhD at NII, Delhi, Qadri moved for his post-doctoral research to the University of Texas’s Southwestern Medical Centre, Dallas. After finishing his research, he flew back to the NII where he had a job.

“In PhD, my focus was to create monoclonal antibodies that would help in swift diagnosis in typhoid cases,” Dr Ayub said. “We did create these antibodies and in clinical trials, these antibodies helped reduce the diagnosis time from 72 hours to less than 24 hours.” However, there was not much follow up and this technology could not move beyond. Off late, however, there is some interest in that now. Besides, he also studied the system of interaction between the pathogen and the host in the case of typhoid.

In his post-doctoral research, Dr Qadri’s focus remained on understanding how the T-cell (immune cells) receptors interact with ligands in auto-immune diseases. After spending two years in the US, Qadri flew back to his immunology laboratory where he supervised various types of research till April 2022, when he moved to IUST.

A Futuristic Centre

In coming years, more fellows are expected to join the centre getting fresh flood and ambitious young men and women with enough resources. Its location is also important because in coming years, it will be the closest research centre to the upcoming AIIMS and there can be a lot of collaborative studies.

It is interesting that the WCCMM’s location has linked contemporary Kashmir with the past of the place and the world, at least metaphorically. The centre is named after two scientists, James Watson and Francis Crick, who are credited for the 1953 discovery of the double helix, the twisted-ladder structure of deoxyribonucleic acid (DNA). That discovery marked a milestone in the history of science and gave rise to modern molecular biology.

Interestingly, the IUST is located at Awantipore, the capital of Kashmir at the peak of the Hindu period when one of the best builders, Awantiwarman was ruling Kashmir. Interestingly, the centre operates from a building named after one of Kashmir’s great saints – whose mausoleum is not far away from the campus, Syed Mantaqi Memorial College of Nursing and Medical Technology. What adds more big names to this centre is that all the three scholars who operate the centre and those who would be joining in the coming days, are funded under Ramalingaswami Fellowship or Ramanujan fellowships, the two highly competitive fellowships named after two great Indians, medicinal researcher Vulimiri Ramalingaswami (1921 –2001) and mathematician Srinivasa Ramanujan (1887-1920).

A group photograph of scientists and research scholars of Watson and Cricks Centre for Molecular Science (WCCMM) at IUST in Awantipore. KL Image: Bilal Bahadur

The IUST, like KU, has a positive environment for innovation and research. Its innovation and incubation centre has done well in the last few years. It has many patents to its credit. The formal entry of high-end scientific research is a huge quantum jump for a campus that started with shrine donations initially.

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