‘Genetics May Help Humans Live A Long Life’

From a south Kashmir school to Canada’s Laval University, Dr Abdul Wajid has dedicated his research career to a better understanding of genes. To his credit is the discovery of a novel role of protein, Kinase CK2 in chromatin modulating processes. Currently heading a vertical at the University of Kashmir’s CIRI, he details how advanced genetics is going to help humanity address some deadly diseases and live slightly longer

KASHMIR LIFE (KL): How widespread is the field of genetics with respect to research?

DR ABDUL WAJID (DAW):  A lot of work has been done in this field so far and much is yet to be done. If you look at the work going on at the Centre for Interdisciplinary Research Institute (CIRI), you might think that every laboratory is working on the same subject. But, things are quite different. There is a lot of diversity in the field of genetics. Everyone is aware of the fact that DNA stores genetic information. But how this information is decoded is basically our area of research interest.

If we look at our body, all the cells possess the same DNA but they look and work differently. Lung cells, liver cells and neurons from the same individual contain the same genetic information, but they are regulated differently in a controlled manner, which leads to different phenotypes and helps to determine which function a cell will have. This differential regulation of genetic information is determined by the organisation of DNA within the cell. In eukaryotic cells, the DNA is packaged in the nucleus as Chromatin. DNA packaging into chromatin has profound effects on gene expression. Cells use different mechanisms involving various proteins to alter the chromatin structure and change gene expression. This is how one cell is a lung cell and another is a nerve cell but has the same DNA.

KL: Will you please take us through your educational journey?

DAW: I started schooling in my hometown, Tral. For my bachelor’s, I went to Amar Singh College, Srinagar. Thereafter, I joined the University of Kashmir’s Department of Biochemistry for my master’s. Subsequent to my post-graduation, I worked as a junior research fellow in one of the most prestigious institutes of India, the Indian Institute of Sciences (IISc) Bangalore. Then I joined Laval University in Canada to pursue my PhD. To continue my research work I joined as a postdoctoral scholar at the University’s Cancer Research Centre. Eventually, in my third year of post-doc, I got selected for one of the prestigious research programmes as a Ramanujan Fellow at the University of Kashmir.

KL: What was your doctoral research all about and what were the takeaways?

DAW: I precisely focussed on how the large stretches of DNA within the nucleus are organised in the form of chromatin and how this organization is important for the tight regulation of gene expression.

The process of transcription includes various steps including initiations, elongation and termination. Earlier, the initiation step was considered a rate-limiting step for the regulation of transcription. Later, it was discovered that transcription elongation is also critical for the tight regulation of gene expression.

Transcription elongation involves a large number of factors whose function and mechanism are poorly understood. They can be classified into two major categories. The members of the first class stimulate the polymerisation reaction by RNA polymerase. The second group of factors do not stimulate directly the reaction but travels with the elongation polymerase and affects other processes including changes in chromatin structure. We studied various factors that have been found to be associated with transcription elongation machinery, the change in the chromatin structure and consequently regulating gene expression. We found that any perturbance of such processes has detrimental consequences on the cell.

KL: What was the global status of this research field at the time you were busy with your PhD?

DAW: Back then, this field of research was at its peak. By the time I started my journey as a PhD student, the focus had already shifted to the transcription elongation step and a good number of laboratories around the world were working and discovering proteins involved in the regulation of transcription. Chromatin structure needs to be modulated during transcription elongation. Different mechanisms and proteins involved in this process were identified during this period by various research groups around the globe. One interesting observation was that chromatin structure is fully restored to its original form after each cycle of transcription.

Dr Abdul Wajid, a molecular geneticist, at the Centre for Interdisciplinary Research and Innovation (CIRI) at the University of Kashmir. KL Image: Bilal Bahadur

KL: What was the takeaway of your post-doctoral research?

DAW: We continued with the subject of chromatin dynamics. We focussed on how the integrity of chromatin is maintained during gene expression and during DNA damage repair. Some of the processes and the proteins involved in chromatin dynamics during gene expression and DNA damage repair are the same and these processes are highly conserved throughout eukaryotes.

KL: What lesson did you learn from your laboratory while working in Canada?

DAW: There are a lot of positive things and lessons learnt. I was positively influenced by the simplicity and generosity of the well-known professors in the field who were always one call away for help. Discipline, hard work, teamwork and integrity in the workplace is the key to success in research.

KL: I am very curious to know if there is any latest breakthrough in the field of genetics apart from CRISPR-Cas9 technology.

DAW: I believe that CRISPR-Cas9 technology is a revolutionary technique. This technology enables geneticists to alter the genome precisely at the desired locus. Now geneticists can modify specific genes while sparing others.  This genome editing technology has extraordinary advantages in various fields. In the coming years, we expect to use this technology to potentially prevent or cure genetic diseases. Many incurable genetic disorders can be cured using CRISPR-Cas9 technology.

KL: Can genetics ever help humans to become immortal?

DAW: With the help of genetics, the longevity of human age is possible as it has been reported that human life expectancy can be prolonged by lifestyle changes and by introducing variations in genes that are associated with ageing. CRISPR-Cas9 technology has been successfully used to delay the ageing process. However, there is no direct evidence of making humans immortal. It is all utopian.

KL: What is your subject and the current status of your research work at CIRI?

DAW: I started to work at the University of Kashmir in my field of expertise. As I already mentioned, the information stored within the DNA needs to be decoded and expressed. The DNA in a cell is organized in the form of a nucleoprotein complex called chromatin, which is a highly complex structure. The protein associated with chromatin helps in the compaction of DNA within the cell and eventually protects the DNA from damage and regulates its expression.

During gene expression, the chromatin structure is loosened and transcription machinery gains access to genomic DNA and ultimately transcription is promoted. Cells have developed mechanisms involving different factors that deal with this challenge and help the transcription machinery. When the transcription step is terminated, it is very important for the cell to restore the chromatin structure to its original form. If chromatin fails to get re-established, it leads to many harmful consequences on the cell. So, chromatin modulation associated with transcription elongation involves chromatin disassembly and reassembly. Interestingly many proteins play a role in both these processes. Our area of research is to understand the mechanism of chromatin dynamics during transcription elongation and how various proteins regulate this process.

Q: What kind of research work your scholars are undergoing?

DAW: As I discussed earlier, various factors are associated with chromatin dynamics during transcription elongation. One such important factor involved in the regulation of chromatin structure is histone methyltransferase Set2, which is the focus of research of one of my PhD scholars. Set2 protein is involved in chromatin refolding/reassembly after the transcription elongation and its regulation is not fully understood.

Another scholar is working on ATP-dependent chromatin re-modeller. Yet another scholar is working on Protein Kinase CK2 whose direct role in chromatin dynamics formed part of my PhD thesis. At that time various proteins were extensively studied, which are associated with chromatin refolding. However, the mechanism regulating the function of these factors was not known. I, for the first time, found that the protein Kinase CK2 regulates these chromatin-modulating factors.

Our scholars are using budding yeast to study how chromatin organization is established, propagated, maintained, and changed during various cellular processes.

KL: Do you have the same level of laboratory infrastructure when compared with the labs from where you have been trained?

DAW: Initially, it was quite a struggle to work with limited resources and infrastructure but for the past three years we have seen a huge improvement and we hope that it could get better in the coming years. In the last couple of years, we at CIRI have secured big infrastructure grants worth crores of rupees. It will speed up our work and increase our productivity.

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