Dr. Hiyaa Ghosh is among eight scientists to be named part of EMBOs Global Investigator Network for 2021.
Read More about Hiyaa's research here
Arunita Banerjee (https://www.arunitabanerjee.com/) caught up with her recently, and here is what Hiyaa had to say.
Please tell us about your academic journey. Why did you choose to pursue science, how does life change when you ascend from being a research scholar to a young faculty, what attracted you towards a career in science, what fascinates you about your current field of research and how has the journey been so far?
Science was always interesting to me because it answered many of my ‘why and how’ questions. But, a career in research was not a pre-decided one. My first taste of the joy of ‘discovery’ (of course very small ones) was during my MS-thesis dissertation. That was when I figured that posing questions that I could test in a laboratory totally thrilled me. The results, however incremental in providing clarity to my questions, were quite exhilarating as it would lead to designing the next set of experiments with the hope to get further clarity. So, the process is like a chain reaction where the pockets of anticipation and excitement was continual and the joy of putting the pieces of the puzzle together was never-ending.
A career in research for me was attractive for many reasons; apart from the constant excitement as I just mentioned, it is also a field which allows you to contribute to the existing knowledge pool, where you not only make use of what is known, but also create information that may even make its place in the textbooks someday, thereby adding to the knowledge pool. I also love the intellectual freedom one enjoys in a research career. Once you are able to convince the funding agency of the importance and relevance of your question, you have all the freedom in how you want to go about it. An additional positive effect is that you get the opportunity to constantly work with the young crop of new researchers (your MS, PhD and postdocs students), and to, hopefully, positively influence their learning and training. So, not only do you get the excitement of making discoveries, you also get the privilege of teaching the next generation of students who are to take science and its excitement forward.
The complexity of the brain has always been very fascinating, however the emerging theme of diversity within a particular cell-type and how it plays into the complex functionality of the neural circuits and brain function is going to be the challenge to solve in the next decades. My journey so far has been very rewarding; I was able to follow my interests at every step of my career regardless of the definitions that demarcated different fields of biology. I worked on cell-signaling during my PhD, moved to immunology and animal model-systems during my post-doctorate at Columbia University, and then carved out my niche in neuroscience while starting my own laboratory here at the National Centre of Biological Sciences, Bengaluru.
The diverse training during my early career allowed me the ability to see across different sub-fields of biology and gain from having an ‘outsider’s perspective’ on many occasions. I truly believe that this is the time of interdisciplinarity, wherein along with the depth, one also needs a wide perspective to answer questions effectively and make significant contributions.
Through your personal journey, what similarities or differences did you find in the research landscape of India and the United States, with respect to infrastructure, work ethics, professional working dynamics and overall atmosphere?
The beauty of science and arts, as you know, is that it is not limited or defined by geography. However, as you correctly point out, the infrastructure and work-environment make a huge difference to the ability of the researcher to perform. When I moved from New York to Bangalore, the one place where I didn’t feel much of a difference was my work place, NCBS. Although I had to build a lot of infrastructure from scratch for my lab, starting from wet-lab to mouse behavioral set-up, everything was possible because the system helped me. Our dean at that time was Prof. Bhalla, who was very supportive and ensured that I could set up what I needed in good speed. The setting up took a couple of years, but this initial support went a long way in what my group could achieve in the next 3-4 years.
There are some inherent challenges though for doing research in this corner of the world; mainly two: the lack of ‘critical mass’ for any given field of research, and the difficulty in procurement of equipment and reagents. One has to plan months, sometimes, years in advance to procure what one needs for an ideal experiment. I understood this in the first year, and planned multiple parallel threads way in advance, some of which ran with a planning of a few years in advance. One needs to anticipate the different direction(s) their results may take them in the future to the best of their ability, and initiate plans in a staggered manner, so that as you hit one milestone, you already have the next step’s ‘preparatory work’ done.
Since your lab maintains a stock of live animals and most experiments are in-vivo (happen inside these animals), how did the lockdown due to COVID19 affect research progress?
Like I was mentioning, the burden of long-term planning comes specially for laboratories that work with vertebrate animal models, like ours. My lab uses complex transgenic mouse lines, some of which are triple and quadruple transgenics—this means it takes a long time to generate the required genetic combination (genotype), and then of course the experiments are to be ideally matched age, gender and litter wise. So, essentially, our animal breeding takes a lot of planning and seeding time, to get useful experimental animals in time. If any of these plans get obstructed, we are set back for months, and in some cases years, for example in long ‘time-point’ experiments, where we collect data from aged animals. The COVID-19 related lockdown and subsequent headcount cap at work place posed a lot of delays in our work. We lost some time-point experiments, and some of our breeding lines were also severely affected, some of which took more than a year to come back to normal. But thanks to my students, who worked as a team during the semi lock-down time, and did everything they could to manage and squeeze out as much data as possible from their remaining samples and animals. Also, our long-term planning strategy came in handy since we had some threads running in the background, which we could focus on, while waiting for the affected lines and experiments to be revived. So, despite the losses, in the end, we made it work.
Does the primary theme of an academic institution (medical science/ fundamental research) have a role to play in determining the outputs from research in neurobiology, cognition and other associated fields in the public health domain?
The primary mandate of NCBS is to do fundamental research in basic biology. I think it definitely helps because this mandate allows us the intellectual freedom to investigate basic biological processes in the context of the laboratory’s research questions, without having to worry about an immediate translational outcome. While translational outcomes are important and relevant to some of our questions, the fundamental understanding of biological processes often lead to intriguing and novel revelations that set the right path for future translational research. My lab is interested in understanding the genetic regulations that allow normal functioning of different cell-types in the adult brain. The outcome of our discoveries so far has uncovered some unanticipated revelations about fate potential and regulatory pathways of cells in the adult brain. These revelations are likely to pave the way for setting new directions in the field of neuroinflammation and neuronal maintenance, both of which are relevant to translational neuroscience and public health. So, while the mandate of NCBS allowed these fundamental discoveries to be made, the same mandate allows us to now take it either in a more translational direction or choose to dig deeper into the mysteries of the machinery inside these cells.
What are some of the open questions about the human brain that your research team is trying to answer presently? How do you expect your research to influence therapeutic advancements concerning neurodegenerative diseases, in the near future?
Under the larger theme of investigating genetic regulations underlying normal cellular functioning of brain cells, we focus on adult neuronal maintenance, and fate regulation of some of the renewing cell-types in the adult brain, such as the neural stem cell and microglia. Our curiosity is in uncovering more about the genetic blueprint that lay in the DNA in a cell-specific manner in the brain, so as to understand what all these cells are capable of doing, and what machinery drives their normal functioning. For example, in our recent studies we have identified that the neural stem cells of the adult brain have a dark side that can lead to inflammation in the brain. In another study, we revealed a large gene-network that underlies the normal activity and structure of adult neurons. A large fraction of the revealed gene-network belonged to a category of genes that were not referred to in the context of neuronal activity earlier, but instead in cellular motility and sensing in other organs. Our report now opens up a whole new way to think about neuronal structural regulations in the adult brain. These fundamental discoveries about the inner machineries in the brain cells allow for more informed investigations of the potential triggers for neuroinflammation and neuronal maintenance in the adult brain, and thereby are very relevant in the context of both cognitive as well as neurodegenerative disorders.
An important question is that of cellular heterogeneity within different cell-types in the brain; why is this diversity needed and how does it feed into the complex functioning of the brain? This question applies both during the steady-state in a healthy brain and in conditions where there is deviation from the normal, such as in different neuro-pathologies. This is where I hope research from my lab will contribute in a significant manner, looking at not any one, but different types of cells in the brain: the neuron, the glia and possibly the vascular cells.
Higher education institutions in India witness a steep drop-out rate among young women as they proceed towards establishing their careers. How do you maintain a work-life balance? What changes in the Indian academic system do you think could balance the gender ratio among students and faculty of science in Indian institutions?
It is indeed disheartening to see that women have very little support to attain the work-life balance. The fact that women dropout in almost every stream of career because they have to prioritize or choose between home or career is very sad, and the loss is for the entire society. This is not only because women are a much-valued talent pool, but also because how the women lead their lives in our society has a great influence on the next generation, in terms of expectations of equity and accountability that would get set. Our next generations learn from what they observe at home and outside—every example matters and contributes to how the social environment is shaped.
I have been very lucky to have a progressive-minded family, who have always supported me. I could not have done any of it without the constant support of my husband; our responsibilities have always been equally important and shared. Also, being in academia helped, given the flexibility it allows. There are some very obvious changes that can ensure equity in opportunities in Indian science. One would be removing age-constraints for women, given that they often have to take time off for child bearing right at the peak time of their career. While merit-based evaluation should never be compromised for gender equity, the due consideration for the lost time for women needs to be accommodated in a more realistic manner. Many European agencies have been able to do this in a reasonable manner. The other change would be to ensure adequate representation and turnover of women in positions of power, be it locally within an institute or at a larger scale across institutes and governmental agencies. Very often the voice of a single woman is often lost in the overbearing male-dominance of our societal existence. Therefore to have multiple, if not equal, representation at places of decision making and other consequential positions, would greatly help in not only providing equal scope, but also setting the right examples.
The EMBO Global investigator award recognizes scientific excellence displayed by young scientists worldwide. How do you expect this prestigious recognition to enhance your academic journey?
I am humbled and delighted to be recognized by the EMBO-GI award. I am hoping that this award will enable me to foster more collaborations across continents, and bring in more diversity in my research group and capabilities. I also hope that this recognition will help showcase that world-class research in genetics and neuroscience is possible in Indian laboratories.
What would be your word of advice to young students of science who hope to pursue a career in scientific research?
Rather than advice, I would like to share my excitement that this is the perfect time to engage in a scientific career, and even more so in biology. With the progress in various technologies, be it in imaging or genetic manipulations or peeking into the DNA blueprint, or manipulating and using biomolecules, so much more is possible in these times, that the sky is literally the limit to what one can go after. Breakthrough discoveries in biology are going to dominate the next several decades in science, making it a good reason to engage in biological research. The other thing I would like to mention is that exposure can shape one’s thought process in ways that one can’t imagine. So, do not hesitate in reaching out for every opportunity you get to find out more about a ‘research career’. Apply for internships, engage with people who do science for a living, visit institutes, ask your schools and colleges to bring in scientists to give a talk or explain the current state of a research career in India or abroad. These efforts will enable you to make informed choices about your career. Finally, science is a rewarding career if one is looking for intellectual freedom, flexibility, creativity and endless scope of growth in one’s future career. There is practically no downside in a scientific research career as per my experience, plus the joy of discovery matches nothing else.
Congratulations Hiyaa! We look forward to your upcoming discoveries and insights, and hope this award will facilitate your research.
More about the award here.