“Failure is not necessarily bad -it makes you tough and mature scientifically”

As part of our International Women’s Day celebrations, we sat down with Associate Faculty Member Priti Agarwal, to learn more about her career highlights, challenges and which female idols inspired her interest in genetics and developmental biology.

Priti Agarwal is a postdoctoral researcher at the Mechanobiology Institute, NUS in Singapore. She works with F1000Prime Faculty Member; Ronen Zaidel-Bar in evaluating the literature relevant to their research interests.

During her PhD at the Indian Institute of Technology Kanpur, Priti developed an interest in the biomechanical signals required for continuous formation of mature oocytes and sperm. This then motivated her to analyze the biophysical features of the C. elegans germline and further, to explore how mechanical forces conjoin with biochemical signals to determine the structure and function of the germline. She joined Dr. Zaidel-Bar’s lab to achieve this goal.

How did you get involved in your field of study?

My graduate research was focused on the germ cell development in a well-studied genetically tractable model organism Caenorhabditis elegans, a free-living nematode. Germ cells are the cells which undergo a specialized type of differentiation known as meiosis to form mature gametes – oocytes and sperm. Successful meiotic differentiation of germ cells is crucial for gametogenesis. In an attempt to identify the key molecular players of meiosis, my study uncovered the novel role of an RNA-binding protein GLD-1 in the meiotic differentiation of male germ cells.

During the first four years of my Ph.D. I started several projects which did not progress much further. So, in essence, I had to ‘re-start’ my Ph.D.! But in hindsight, I feel that failure is not necessarily bad. It makes you tough and mature scientifically.

While studying the role of biochemical signals, I became interested in biomechanical signals required for development.  I wanted to transition from a gene-centric to a more holistic approach for understanding development that also takes into consideration biophysical aspects of cells and tissues.  Towards this aim, I joined Dr. Ronen Zaidel Bar’s lab at Mechanobiology Institute, NUS, Singapore and studied biophysical features of the C. elegans germline and explored how mechanical forces determine the structure and function of the germline.

What do you most enjoy about your work? 

The thing which I enjoy most about my work is that I get to learn something new every day- whether it is by carrying out experiments on the bench, looking through the microscope, reading literature or attending a lecture. I really enjoy using interdisciplinary approaches to solve the problem at hand. It provides me with a wonderful opportunity to interact and collaborate with different people expertise in their respective area of research. It often stimulates a new perspective and also helps in testing a hypothesis which otherwise would be difficult to investigate using a single traditional approach.

For example, for our recent publication, we collaborated with theoretical physicists who developed a qualitative 3D vertex mathematical model that simulated the balance of forces within the gonad and demonstrated how the changes in the contractility of apical actomyosin corset are sufficient to drive the changes in germline morphology as we observed in our experimental results.

What is the biggest challenge that you have overcome?

During the first four years of my Ph.D. I started several projects which did not progress much further. So, in essence, I had to ‘re-start’ my Ph.D.! But in hindsight, I feel that failure is not necessarily bad. It makes you tough and mature scientifically. So, when I began a new project after four years, I was more confident and started to reward myself with small celebrations whenever an experiment as trivial as a routine PCR worked. I changed my perspective for my first few years from a ‘non-productive period’ to a ‘rigorous training period’, convinced in my mind that those years invested in the lab would go a long way in steering my scientific thought process in the right direction.

The thing which I enjoy most about my work is that I get to learn something new every day- whether it is by carrying out experiments on the bench, looking through the microscope, reading literature or attending a lecture.

Do you have any idols who inspired your career?

I am deeply inspired by the significant contribution of Christiane Nüsslein-Volhard in the field of developmental biology. She carried out a mutagenesis screen to identify genes involved in patterning and segmentation in the embryo of Drosophila melanogaster. For this work, she was awarded Nobel Prize in Physiology in 1995. She also established Zebrafish as a model organism for studying vertebrate embryonic development.

Although I may be a bit biased, I have also been inspired by several female scientists who did pioneering research using Caenorhabditis elegans as a model system. To name but a few, Cori Bargmann, a neurobiologist at Rockefeller University, was first to discover olfactory sense in C. elegans. She identified the molecular and neuronal basis for different odors and their behavioral output. Julie Ahringer, Professor of genetics and genomics at Gurdon Institute, UK, constructed ground-breaking, genome-wide RNAi feeding library which is currently used to silence gene expression across the worm community worldwide. Judith Kimble, Professor in the Department of Biochemistry at the University of Wisconsin-Madison, discovered the germline stem cell niche and studies the mechanism of regulation of stem cell fate and differentiation. Anne Villeneuve, Professor of Developmental Biology and Genetics at Stanford University, is well-known for establishing the C. elegans as a model to study faithful chromosome inheritance during meiosis.

What was your last F1000Prime recommendation?

My last F1000Prime recommendation was a study, “Membrane Flow Drives an Adhesion-Independent Amoeboid Cell Migration Mode”, by Patrick O’Neill and colleagues which explored the molecular mechanism of adhesion-independent cell migration. Using elegant optogenetic tools, authors showed that cells in suspension move by the tangential viscous force generated by a continuous flow of cortical membrane from the rear end to the front of the cell. Cell shape during migration is maintained by polarized endocytic trafficking of the cell membrane.

Adhesion-independent amoeboid cell movement has been observed during embryonic development, immune function as well as during cancer cell invasion. Hence, understanding the mechanism by which different biochemical and mechanical signals directs amoeboid cell migration, as shown by this study, not only helps us in understanding development but might also assist in the innovation of novel therapies for the alleviation of different pathological conditions.

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