In Kashmir: Doing Impactful Science

The shortage of infrastructure was the important thing mind drain issue as researchers would select higher international establishments for doing science. Beneath a powerful plan to make sure ‘mind achieve’, the central authorities began funding one of the best researchers with good concepts to return house and this led to the institution of the Centre for Interdisciplinary Analysis and Improvements (CIRI) on the College of Kashmir as certainly one of Kashmir’s high two new establishments for science, studies Masood Hussain

Some members of the college on the Centre for Interdisciplinary Analysis and Innovation (CIRI) on the College of Kashmir. KL Picture: Bilal Bahadur

It has been a rollercoaster experience for Dr Altaf Bhat. Born in distant Panchpora hamlet in South Kashmir, Bhat studied until his masters within the state-run instructional infrastructure the place English would mark an entry in sixth class. His life was stuffed with surprises after he moved out as a younger biochemist for his PhD in Canada.

within the genetic interaction within the human physique, Bhat was all the time passionate to know how Epigenetic controls human physiology. Epigenetics is a relatively newer science that makes an attempt to hunt solutions to how particular person behaviours or the encompassing ecosystem triggers adjustments that have an effect on the best way genes work. The entire concept is how to make sure reversibility, which is feasible in such circumstances, not like genetic adjustments dictated by inheritance.

DNA, explains Bhat, does undergo injury owing to a assorted set of things, each endogenous and exogenous. “If fast repairing doesn’t happen, the broken DNA will get transferred to the daughter cells thus impacting the entire organic course of and ultimately resulting in totally different ailments,” Bhat stated. “There are specific proteins which have the capability to restore this injury. Throughout my examine, I situated a set of occasions that are obligatory for the recruitment of those proteins to the restore websites and as soon as the injury is repaired then these elements should be launched.”

In sciences, a PhD is invariably seen as high-end subtle coaching. Actual science truly takes off from the post-doctorate degree, although there are numerous circumstances during which the intense minds had extra high-impact papers to their credit score even on the PhD degree.

From Canada, Bhat took off for a post-doc at Harvard College in Boston the place he spent 4 years in analysis. Not transferring away from his core focus, Bhat began trying to find solutions to an enigma about how and why a sure genome is localized on the periphery whereas some a part of it’s current inside the nucleus. “We already know that DNA isn’t current within the cells randomly and follows a particular form and a specific configuration, which is vital to its functioning,” Bhat stated. “I studied the mechanism that positions DNA at varied elements of the cell and whether it is interrupted, the way it impacts the functioning of various kinds of cells current in varied organs.”


Bhat’s analysis was in continuation of an intense genetic debate about how cells at their very own degree retain their identification and autonomy to a degree whereas being half of a bigger mechanism the place the mind is the last word decision-maker.

By 2013, Bhat was again house, now as an Assistant Professor. Since 2019, he’s the Coordinator of the newly established Centre for Interdisciplinary Analysis and Improvements (CIRI) on the College of Kashmir, which is predicted to be one of many two new addresses for the high-end cutting-edge science in Kashmir.

The CIRI is the result of the Authorities of India’s main coverage intervention on how to make sure mind achieve. For the final greater than six a long time, the higher minds would search areas within the growing world, apparently due to higher infrastructure, superior analysis local weather and higher earnings. The federal government of India constituted two main fellowships – the Ramanujan Fellowship (piloted by the Science and Engineering Analysis Board) and the Ramalingaswami Fellowship (Division of Biotechnology) for vivid scientists eager to return house so long as they’ve one of the best concepts to work on. They’re supplied with sufficient funds to pursue their analysis and after 5 years, they’re adjusted as college. Since 2006, when the Ramalingaswami Fellowship was launched, greater than 550 biotechnologists have returned house to put the muse of a strong biotechnology vacation spot in India.

Within the final three years, CIRI has acquired six scientists below the dual fellowships. They’ve labored in one of the best analysis establishments on the earth and at the moment are eager to encourage analysis. “CIRI serves two issues – to develop a wealthy interdisciplinary analysis ecosystem within the College of Kashmir, to deal with scientific issues by a multidisciplinary or interdisciplinary method and likewise to develop world-class scientific infrastructure in order that our younger scientists have an entry to the state-of-the-art know-how to do high quality scientific analysis,” Dr Bhat defined. “Within the final two years, we have now succeeded in securing Rs 40 crore from totally different funding businesses to deal with varied biomedical issues prevalent within the area and likewise to develop scientific infrastructure within the institute.”

CIRI is predicted to be a serious centre within the coming days, Bhat stated inside a 12 months or so CIRI might be at par with the Harvard or Massachusetts Institute of Know-how (MIT) so far as infrastructure goes. This 12 months, CIRI is taking round 10 PhD college students. “The college goals to carry round 25 Ramanujan, Ramalingaswami fellows in a 12 months or two in order that it offers a push to the interdisciplinary method,” added Bhat.

Robust Foundations

Organising of CIRI, nonetheless, doesn’t essentially imply that science was not being achieved within the College of Kashmir. The departments of biotechnology, biochemistry, and pharmacy are dominating the general Kashmir science pool as a lot of the scientists have had their primary training on this chain of departments. Whereas the main target remained on basic research, the analysis, off late, has taken off.

Mohammad Ashraf Dar was one of many biochemists that the division educated. Hailing from Chanpora in Bejbehara, Ashraf was all the time fascinated by the proteins because the constructing blocks, info codes and the workhorses of the cell. Publish-masters, he moved to JNU and did his analysis on plasmodium, the malaria-causing pathogen. “Throughout my analysis, I found a novel protein within the parasite, known as DNA gyrase that, we understood, is principally controlling the DNA replication technique of the pathogen,” Dr Ashraf stated. “Later, we even recognized the drug – Acriflavine, that inhibits this Malaria particular gyrase and this found led us to a world patent.”

After PhD, Dr Ashraf moved to the celebrated Mayo Clinic’s Biochemistry Division at Rochester. There, he pursued analysis on understanding chromatin biology. For the subsequent 4 years in 2011, he joined the College of Virginia as a analysis affiliate scientist. “There, I found USP46 (ubiquitin-specific protease 46) as a possible drug goal in cervical most cancers. I elucidated out the molecular mechanism by which human papillomavirus hijacks host’s personal protein (USP46) to advertise cervical most cancers,” Dr Ashraf stated. “Synthesising drug molecule in opposition to USP46 will open up therapeutic regime in opposition to this most cancers and can set an alternate path to the a lot deadly radiation remedy.”

By then, he had sufficient experience and publicity to use for the Ramalingaswami Fellowship, which he acquired within the first go. Now his laboratory is engaged on totally different features of ubiquitin, a regulatory protein present in almost all eukaryotic organisms and is nearly similar throughout all types of life – human, yeast, and plant. “We’re engaged on this ubiquitin molecule in numerous contexts and its relevance to numerous points together with DNA injury, apoptosis, autophagy and most cancers.”

Attention-grabbing Struggles

Each one of many scientists who has include a grant to CIRI has an attention-grabbing story of particular person wrestle and success to his credit score. All of them have struggled of their lives and now want to set up the centre because the nucleus of doing science on the College of Kashmir.

Dr Aijaz H Wani is certainly one of them. Hailing from Dakhum, the picnic spot and the final Kashmir village on the street to Kishtwar, Aijaz studied in native state-run colleges and did his grasp’s in biochemistry from the College of Kashmir. For PhD, he joined the Nationwide Centre for Organic Sciences on the TATA Institute of Basic Analysis in Bangaluru.

“I opted for Protein Biophysics and needed to know why the proteins have basically to retain a 3D construction to remain related and energetic,” Aijaz stated, speaking about his PhD. “I discovered the proteins to be extremely dynamic however needed to know the elements that decide its 3D shapes and the way they’re related to its functioning.” Utilizing mass spectroscopy, many new issues have been revealed to Aijaz throughout the analysis. He discovered that typically proteins mixture in conditions apart from section segregation, and set off a degenerative illness like Parkinson’s illness.

When Aijaz moved to Harvard for a post-doctorate, he opted for a ‘quantum bounce’ and determined to get into genetics. He had, like many different scientists in numerous laboratories, one query to hunt a solution to: “How does a cell construction barely a number of microns measurement handle to accommodate the DNA that’s even two million occasions longer than it?” Then there have been associated points about if the peculiar packaging is disturbed within the cell, and the way it reveals its affect on the human physique.

“Utilizing very high-end know-how, we might see that proteins play a key function on this packaging and any disruption in it manifests in skeletal deformities,” Aijaz stated. “We have been engaged on it when some Japanese scientists got here with a lot clearer solutions that it impacts rib cage and lots of different issues.”

The genome ultimately fascinated Aijaz a lot that he wrote a undertaking that Welcome Belief (UK) and DBT authorized and gave him a grant of Rs 3.5 crore for additional research on the identical topic in 2017.

“My group of researchers are addressing the identical query, the packaging however we are attempting to establish different proteins that contribute to this,” Aijaz stated. “We have now some excellent leads and we’re engaged on some molecules and shortly we might be out with what we have now discovered.” They’re additionally taking a look at how sure ailments are linked with the disturbance within the DNA packaging of the cell.

Although it’s already identified that faulty packaging will be inherited and that the genome isn’t perpetually insulated from the surroundings it exists inside, Aijaz’s group can be making an attempt to see how genome mutations are linked to meals habits and different elements that an eco-system provides.

Understanding Genome

At CIRI, there’s one scientist who has labored on proteins alone for his total analysis profession. It’s believed that the human physique has a set of virtually 100 thousand proteins however science is aware of nothing past 20,000. So each laboratory throughout the globe is within the race to know the proteins higher as these are the workhorses and the constructing blocks of life. Dr Javaid Yousuf is certainly one of them.

Hailing from Dialgam belt of South Kashmir, Javaid Yousuf studied biotechnology on the College of Jammu after which moved to Jawaharlal Nehru Centre for Superior Scientific Analysis (JNCASR), Bangaluru for his PhD the place he labored on Malaria with a give attention to discovering the similarities and dissimilarities between a specific enzyme that exists within the human physique and the Malaria creating Plasmodium. That analysis undertaking, Yousuf stated remains to be happening in that laboratory and now has reached the drug discovery stage.

His main publicity to superior science was within the seven years he spent at Max Planck Institute of Biochemistry, Munich, in Germany the place he centered on protein chemistry. “Essentially the most plentiful protein in nature is Rubisco, which types virtually 70 per cent of the whole protein in crops, however we didn’t know the way it may be made outdoors the crops for biotechnological functions,” Yousuf stated. “My small contribution was to find that there are a selection of proteins that assist in its making and we ultimately efficiently demonstrated in E. coli the pathway wanted for its technology and correct perform.”

In addition to, he labored on chaperone proteins, that are basic to conformational folding or unfolding or modulation of huge proteins or macromolecular protein complexes. “These are like go-betweens; they assist totally different protein molecules to get nearer to one another and as soon as this process is over, they transfer out and go for one more process,” Dr Yousuf stated.

Nicely educated in mass spectrometry and different protein evaluation methods, Yousuf moved to King Abdullah Analysis Institute in Riyadh however returned house inside a 12 months, as his proposal was accepted by the DBT, India. At CIRI, his group remains to be engaged on the chaperons as it’s now absolutely established that these sub-super microscopic king-makers flip right into a catastrophe if even one of many amino acids inside them adjustments. On the similar time, his group is learning the immunity and defence response about and round chaperons to ailments in rice with the hope that if they can perceive the mechanism, it’d assist handle ailments in varied business crops.

The Parkinsons Illness

CIRI has a full-fledged group engaged on the totally different information of Parkinson’s illness (PD) by Dr Rafeeq A Mir, one other south Kashmir biochemist scientist who has been engaged on it for greater than a decade now. “We don’t have clear knowledge accessible in regards to the incidence of the illness in Jammu and Kashmir however a broad estimation is that in each one lakh inhabitants that has crossed the age of 60 years, we will need to have 250 sufferers,” Dr Mir stated. “The large use of pesticides should be including to this quantity step by step however there is no such thing as a clear knowledge.” Dr Mir stated that the science has already established that PD is genetic in nature in merely ten per cent of the case and within the remaining circumstances DNA mutations happen due to exterior elements and pesticide use might be a serious contributor. It’s, in spite of everything, an age-associated mind dysfunction affecting the perform of the nervous system inflicting uncontrollable actions, shaking and many others.

Mir has been engaged on points associated to PD for a very long time now. “In my post-doctorate, I’ve found a breakthrough the place we have now proven two elements (proteins) work in live performance and are essential for Parkinson’s Illness improvement,” Dr Mir revealed about his post-doctoral work at Mir later moved to the UK for his post-doctorate at Medical Council UK.

His PhD, on the Indian Institute of Science Schooling and Analysis (IISER) Pune, nonetheless, was round colorectal most cancers, which is triggered when cells within the gut lining or rectum develop abnormally. “In my PhD, I’ve found that SATB1 vital molecule required for packaging of DNA inside cells is essential for colorectal most cancers improvement by selling cell development and spreading of most cancers cells,” Dr Mir stated.

Again house his group is knowing mechanisms underlying PD, particularly figuring out novel molecular gamers and epigenetic modulators to find signalling nexus that could be key in growing the illness. “We make use of varied biochemical and molecular instruments together with in vivo methods to deal with these questions,” he stated.

Molecular Genetics

Interacting with the CIRI scientists offers an impression as if each scientist is engaged on genetics. Although it’s a truth, the bigger actuality, nonetheless, is that everyone has his sub-domain. The two-meter DNA is so sophisticated a construction that even after managing to sequence it, science barely is aware of solely a little bit of it.

“At one time limit, we have been instructed that the transcription initiation is crucial step in gene expression and as soon as it takes place there is no such thing as a regulation over the method,” Dr Abdul Wajid Bhat, one other biochemist at CIRI stated. “However now it’s established that the transcription elongation can be very crucial as a result of if the chromatin doesn’t restore itself to the unique standing after the method, the cell is doomed.”

Bhat, a scientist from Dadsara in Tral, did his grasp’s from the College of Kashmir and moved to the Indian instate of Science Bangalore as a scholar in Molecular Biophysics. He did his PhD from Laval College Quebec in Canada and flew house after his post-doctorate there. In his PhD, he decided a brand new perform of a protein that helps within the technique of gene transcription and restoration of chromatin construction, a topic he studied additional in his post-doctorate.

“It’s a very sophisticated course of and we tried to establish the elements that play a job in serving to chromatin to revive to its unique place after the data is expressed /transcribed,” Dr Bhat stated. “The larger thriller in all the course of is how the chromatin retains its integrity after its info is decoded.” The topic, he stated, is being investigated by virtually each main laboratory throughout the globe as a result of it’s the new factor in genetics.

“My group of researchers is engaged on the identical topic – how genes specific, how they decode, what are the issues of the method and which elements assist chromatin retain its integrity,” he stated. “A defect on this course of has dramatic penalties for mobile capabilities and underlies many ailments.” His laboratory is utilizing budding yeast to check how chromatin group is established, propagated, maintained, and adjusted throughout varied mobile processes.

 Chemistry Laboratory

The centre has a powerful infrastructure and inside a 12 months it’s anticipating a few of the finest machines it requires for analysis. Nonetheless, it nonetheless is in its infancy. Although biology dominates the scene, scientists have began coming from numerous fields to affix for analysis. Chemist Gulzar Ahmad Bhat is the youngest scientist from Kurhama Ganderbal who joined CIRI after his post-doctorate from Texas.

“I used to be the primary to stabilize monoalkyl phosphates, and consequently produced them in multi-gram portions. Utilizing these alkyl phosphate ligands later a brand new household of single crystalline inorganic lamellar copper alkyl phosphates have been synthesized to exhibit how a crystal containing as many as 500 layers will be exfoliated to a single layer nanosheet through a facile and speedy solvent-assisted methodology,” Dr Gulzar stated, about his PhD at IIT Mumbai. “Then, I studied the kinetics of exfoliation, which ultimately revealed that with a rise in sonication time the thickness of nano-sheets will be decreased. Thus, when sonicated for 40 minutes a real single nanosheet of the thickness of 1.2 nm will be obtained, which matches with the thickness of a single nanosheet, as calculated from single crystal X-ray diffraction knowledge.”

Throughout his post-doc at Texas’s A&M College within the USA, Gulzar labored within the space of using CO2 for making biodegradable plastics in a sustainable method and developed a powerful understanding and coaching on this new utilized area of analysis. Again house, he’s establishing the Inorganic and Polymer Chemistry Lab at CIRI, which ultimately will tackle the seize and utilization of CO2 as a C1 feedstock for making biodegradable polycarbonate polymers in a sustainable method.

A Future Tackle

“We hope that extra scientists will be part of within the coming days, “Coordinator, Dr Altaf stated. “In a number of years’ time, the younger scientists will favor working again house as we might be having the state-of-the-art facility right here”.

Nonetheless, the true profile of CIRI will begin constructing with the distinct papers that might be printed by high-impact journals throughout the globe. Aijaz stated that the result of the continuing analysis might be seen in a 12 months or in order analysis is occurring uninterrupted.

Some members of the college of the Centre for Interdisciplinary Analysis and Innovation (CIRI) on the College of Kashmir with the primary batch of analysis students within the 2022 summer time. KL Picture: Bilal Bahadur

On the similar time, the centre is figuring out the native points that it needs to deal with. Dr Altaf stated the prevalence of the non-alcoholic fatty liver illness is a serious problem inside and out of doors Kashmir. “The biology of non-alcoholic fatty liver illness has not been understood by the scientists but,” Dr Bhat stated, revealing that his laboratory is making an attempt to know how epigenetic processes get misregulated or how they contribute to it. “We have now recognized an epigenetic issue which performs an important function. We have now achieved our experiment with totally different cell sorts. In our subsequent section, we are attempting to check this speculation in animal fashions (mice) the place we will induce non-alcoholic fatty liver illness after which take a look at whether or not we will use the recognized molecule as a therapeutic goal to manage it.”

The opposite main researcher in Dr Bhat’s laboratory is to know the biology of Gastrointestinal (GI) cancers in Kashmir.  “Whereas the incidence of GI most cancers globally is round 20-25 per cent, it’s round 50 per cent in Kashmir.”

(Humaira Nabi contributes to the report)

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