Understanding the basic mechanism involved in genes activation can help us answer broader scientific questions regarding human health.

Manisha Jalan, our next pathbreaker, applies her expertise in Molecular biology to bring out the essence of research findings in simpler words that are easily understandable by the general public

Manisha talks to Shyam Krishnamurthy from The Interview Portal about her Post Doctoral work on a rare type of leukemia called, “Acute lymphoblastic leukemia”.

For students, the significance of research is all about expanding the existing body of scientific knowledge which results in a long-term benefit to society.

Manisha, Your background?

I was born in a middle-class family in Asansol, West Bengal, India. My dad is a businessman, and my mother is a homemaker. We are a traditional Indian family who believes in the strong family bonds of a joint family. Hence my childhood was very pleasant surrounded by my grandparents, parents, uncle and aunt, my siblings, and cousins.

As a child, I was always fascinated by Biology. Apart from my growing love for science, I loved sketching and painting. I would use my skills to make biological diagrams more interesting. I always received encouragement from my teachers and my parents. I always wanted to get a deeper understanding of life science. My fascination took me towards my current path.

What did you do for graduation/post-graduation?

I completed my Bachelor’s program in Biotechnology from Manipal Academy of Higher Education. I further pursued a Master’s program in biotechnology from Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham. I continued my formal training as a research scholar at the National Institute of Immunology, New Delhi. I then moved to Ottawa for my postdoctoral training.

How did you end up in such an offbeat, unconventional and unique career?

During my school days, my mother would read books on scientific discoveries to me. I was also lucky to have amazing biology teachers in school. They not only made us understand the mechanism behind each aspect but also left us thinking about how someone came up with these answers. Honestly, when I think about it now, it was my school and mother who ignited my inquisitive mind to follow my current path.

Of course, during my formal training, I started understanding the subject deeper and gained the required information to proceed as a researcher.

I remember the first conference that I attended during my bachelor’s. That event is so close to my heart. I met so many amazing young researchers who were more than willing to talk to students, and their enthusiasm was so contagious that it never left my mind.

How did you plan the steps to get into the career you wanted? Or how did you make a transition to a new career? Tell us about your career path

Although I loved life science and knew I wanted a career in this subject, I wasn’t clear what steps I should follow. There wasn’t any role model. During my bachelor’s and master’s, we had a six-month dissertation program where we had the flexibility to choose our research topic and work under great Scientists. This gave a very clear understanding of how a typical day of a researcher is spent. I loved working on bench troubleshooting experimental designs to get answers to our broad scientific questions.

During my bachelor’s, I worked on a case-control study to find an association between colorectal cancer and a mutation in a gene, SHMT1. This gene is involved in the one-carbon transfer cycle and my study indicated that the mutation is linked to an increased risk of colon cancer in a certain population.

This observation made me more inquisitive to look at the mechanistic role of the SHMT1 protein. I further carried out a biochemical and structural analysis on the protein and its mutants during my Master’s dissertation in IISc, Bangalore. I worked under a highly motivated PhD scholar and learned many techniques including protein synthesis, chromatography, and crystallography. Here, we analyzed different mutants of SHMT1 and found how a mutation in the catalytic subunits can change the kinetics of the protein. This motivated me to further dedicate my career to bench work.

During theoretical training, we were introduced to a subject called epigenetics. I was always intrigued by the fact that not only changes in DNA sequence but even the smallest modification on DNA can have a substantial influence on the phenotype. I then started looking for labs working on epigenetics. 

For my PhD, I moved to a lab that was working on CTCF, an architectural protein and its role in VDJ recombination. VDJ recombination is responsible for B-cell and T-cell diversity. I explored the role of CTCF and other regulatory elements within T-cells in regulating locus conformation. I mainly focused on the T-cell receptor (TCR) beta locus. To explain briefly, the TCR beta locus is involved in the expression of the TCR-beta chain that gets expressed on the surface of T-cells along with the TCR-alpha chain. TCR alpha-beta is involved in the adaptive immune response. I looked at chromatin orientation during murine T-cell development. This was basic molecular biology research. My work help me explore how the nuclear organization within cells can influence cell function. My PhD training further helped me to become an independent researcher.

I moved into more applied research for my postdoctoral training and worked on a rare type of leukemia. I was engaged in several meetings and collaborating with other scientists and fellows. During this time, I realized science is not just having an inquisitive mind but also how well you can communicate your work with the world.

How did you get your first break?

I consider enrolling in PhD as my first break, which shaped me as an independent researcher. After my PhD I started applying for post-doctoral fellowships in labs working on leukemia and I made it into a lab working on T-cell acute lymphoblastic leukemia. 

What were some of the challenges you faced? How did you address them?

The first challenge was choosing the right project. It was overwhelming at the beginning when we were so naïve. I started networking with previous lab members to learn about the lab, project, and their experience. This helped me and then I just went with the flow.

The next biggest challenge that almost everyone faces in this field is “imposter syndrome”. One needs to talk to peers. Only when we share our mental health issues, we learn that we are not alone. We need to trust ourselves!

Where do you work now? What problems do you solve?

My formal training helped me transition to my current role. I am working as a freelance medical writer. Although one does not need a wet lab experience to be a medical writer, a clear understanding of scientific discoveries and an aptitude to stay in tune with recent research help you make a good writer.

I love reading about scientific discoveries and my day is usually spent doing the same, summarizing the articles into simpler words that are easily understandable by the general public.

My expertise in Molecular biology and oncology further helps me to bring out the important essence of research findings.

My postdoctoral was more applied that required all the skills I acquired during my PhD in Molecular Biology.

I worked on a specific subtype of T-cell acute lymphoblastic leukemia. My work required looking at chromatin conformation in leukemic T-cells compared to normal T cells. My Ph.D. background helped me establish the techniques in the new lab. I analyzed leukemia progression using transgenic mouse models. I further looked at the factors that could play a potential role in leukemia development along with the known oncogenes. My work involved cell lines, patient samples, and mouse models. This was a very exciting project, and I was involved in training many students at different levels of their training.

How does your work benefit society? 

As a researcher, our work is not always the greatest scientific breakthrough, however, it adds to the encyclopedia of scientific knowledge. I believe all scientific discoveries have a long-term benefit to society and I am proud to be a part of it.

Tell us an example of a specific memorable work you did that is very close to you!

During my PhD, I worked on a basic mechanism that is involved in genes activation. I used 3D-FISH to show that an activated gene is looped away from its chromatin cluster within the nucleus whereas an inactivated state remains buried inside. This work is further addressed in the lab using different models and shows how dynamic the eukaryotic nucleus is!

Your advice to students based on your experience?

I would say stay focused and choose what interests or motivates you. One can be a very bright student but if not motivated then it’s very hard to strive in any field. If interested to work as a researcher then choose short-term projects in some lab to get first-hand experience. 

Future Plans?

I am planning to move into a full-time medical writer.