Interview with Journal of Cell Science Editor Richa Rikhy Free

Prof. Richa Rikhy

What inspired you to become a scientist?

I have liked science and maths for as long as I can remember. I did not have a scientist in my family while growing up, so I did not have any direct exposure to their passion for the pursuit of discovery, and my interest in research as a profession grew rather slowly. I had to make a decision whether to study biology or maths, because the possibility of choosing hybrid courses and studying these subjects together did not exist in degree courses at that time in India. If it had been allowed, maybe I would have studied a combination of biology and maths, but I chose biology because of the range of interesting concepts involved. Learning various topics in biology as an undergraduate student and compiling notes from different textbooks on cellular processes that were taught in class is something I enjoyed a lot. Among the many topics in biology, I was always drawn to studying genetics and using tools of genetics to decipher gene function as an undergraduate student. I also liked studying genetics and deciphering gene function. The gradual realization that a research career meant that I could keep studying forever, along with having the possibility of making new discoveries in biology through experiments, inspired me to be a scientist.

Can you tell us about your career path so far? What has been the most interesting stage of your scientific career?

I obtained my Bachelor's in Science in life sciences and biochemistry from St. Xavier's College, Bombay, India, followed by a Master's in biochemistry from The Maharaja Sayajirao University of Baroda, India. I then obtained my PhD from the Tata Institute of Fundamental Research in Bombay working with K. S. Krishnan. We studied the mechanisms by which trafficking at the synapse in dynamin-mediated endocytosis affected changes in behaviour, synaptic physiology and synaptic architecture during development in Drosophila. I got very interested in membrane trafficking and neuronal shape remodelling in development during that time; as a result, I found that I really liked microscopy and wanted to learn more.

As a postdoctoral fellow, I worked on morphogenesis and differentiation with Jennifer Lippincott-Schwartz at the National Institutes of Health in Bethesda, Maryland, USA. The freedom and opportunity that the US offers for researchers to pursue what they want is amazing. I was very excited to go to the US for a postdoc in Jennifer's group, which was a completely international lab. Getting to know people from all over the world was a fantastic experience. In Jennifer's lab, microscopy companies would just leave microscopes for us to beta test and try new methods on! I really cherish those years. There, I particularly enjoyed using imaging methods to probe cellular dynamics in the developing Drosophila embryo. We found a role for the recruitment of dynamin, and possibly endocytic function, in specific steps of remodelling of the early epithelial-like cells in syncytial Drosophila embryos and identified the function of mitochondrial dynamics in regulating follicle epithelial cell differentiation in Drosophila oogenesis. These were both very exciting discoveries.

When I started my own lab at the Indian Institute of Science Education and Research in Pune, India, I had so many exciting, diverse ideas. I started doing a lot of imaging with my master's and PhD students, who are typically really young students when they join the lab. We've learned about the onset of epithelial cell-like organization of the early embryo and probed the dynamics and function of subcellular organelles in embryogenesis and differentiation in Drosophila development. More recently, we've looked into neural stem cell differentiation. Working with students and making discoveries through our combined understanding together as a lab has been one of the best experiences and the most exciting phase of my career.

What ultimately drew you toward studying cell differentiation and morphogenesis?

During my PhD, I was attracted to the question of how cells and their organelles acquire morphologically distinct forms and how these forms are related to their function. As a postdoctoral fellow, observing the dynamics of epithelial-like cells in the early Drosophila embryo totally consumed my attention. My current interest in morphogenesis and differentiation emerged partly from my postdoctoral work, and largely from the ongoing work done with my students.

What is the main theme of your lab's research and what questions are you are trying to answer just now?

My lab continues to focus on deciphering the cellular mechanisms that regulate epithelial cell remodelling in embryogenesis and stem cell differentiation. We focus on developing and testing tools for imaging and analysis of cells in vivo in the context of embryogenesis and stem cell differentiation.

We are currently working on screening the roles of various BAR domain-containing proteins in regulating plasma membrane and actin cytoskeletal remodelling in early Drosophila embryogenesis. Many BAR domain-containing proteins are linker proteins, which not only interact with membranes but also modulate the cytoskeleton. They therefore form a very nice link for studying both membrane and cytoskeleton remodelling. This has allowed us to learn more about processes like actin villi remodelling and lateral membrane formation during epithelial cell formation in the early embryo.

We are also studying the role of mitochondrial dynamics and activity in regulating actin remodelling during epithelial cell formation in embryogenesis by conducting a very systematic analysis of the dynamics of mitochondria in the early embryo. We are now starting to ask how metabolites in the embryo influence stages of actin remodelling and epithelial cell formation. By probing the interaction of mitochondria with the endoplasmic reticulum and peroxisomes, we hope to uncover mechanisms of quality control and homeostasis during epithelial cell formation in embryogenesis.

What is your approach to developing new avenues of research?

My approach to thinking about new research questions often starts with observation of a subcellular structure or organelle. For example, in my lab, we have systematically observed the onset of plasma membrane shape remodelling and the organization of the cytoplasm in the early Drosophila embryo. We also recently started looking at the endoplasmic reticulum and peroxisomes and how they are organised in the Drosophila embryo. First, we want to understand the mobility, dynamics and changes in distribution of these organelles. Then, we will often try to either remove the organelles or change their shape or function to see what effect this has on development and cell morphology. The next step, which we are now poised to develop, is systems-level approaches. In the case of mitochondrial, endoplasmic reticulum and peroxisomal mutants, we want to understand how defects in these organelles affect metabolites in the embryo. Going forward, I hope to incorporate physiological and systems approaches with the genetics and cell biology that we've learned to employ in the early Drosophila embryo.

What do you think are the biggest open questions in your field?

In terms of cell and developmental biology, there are several open questions I am quite interested in. First, the mechanisms of interaction at the cellular level between the different cell types that form a tissue are not completely understood – what metabolites or signalling molecules are involved? How axial patterning cues, which communicate information about the emerging body axes and tissue polarity during development, regulate tissue-scale dynamics has also been of great interest to me. Subcellular organelle dynamics are likely to be important for efficient tissue-scale changes, and I am quite excited to see how this question is addressed with the advent of better high-resolution microscopy techniques. Finally, the impact of physiology and metabolism in mediating cell–cell interaction and differentiation is a fascinating emerging area of investigation.

Your research involves advanced live microscopy methods. What do you think are the most exciting recent innovations in imaging for the cell biology field?

Recent advances in light sheet microscopy and structured illumination microscopy have made it possible to image plasma membrane and organelle dynamics in the context of cellular interactions within three-dimensional tissues in developing organisms and organoids. I think these will allow breakthroughs in studying specific processes during development and how different types of cells interact. I look forward to how these techniques will improve our understanding of remodelling events in tissue with unprecedented detail and at high temporal and spatial resolution.

What made you interested in taking on the role of Editor with JCS, and what impact would you like to make in this role?

I have been very impressed by the high quality of papers published by and the broad readership of the journals of The Company of Biologists. When I was invited to be an Editor for Journal of Cell Science, I was immediately excited and responded ‘yes’ very quickly! One of my motivations in accepting this offer was having this very interesting opportunity to learn about more cell biology research firsthand from an Editorial perspective, because of my persistent love of learning. As an Editor, I will strive to uphold the high standards of publishing in Journal of Cell Science. I also hope that I can motivate researchers to submit more papers in the area of cell and organelle shape remodelling in development. I would love to see more research on this in different organisms and in complex three-dimensional models using imaging and genetic manipulation approaches.

How would you like to see scientific publishing change in the future?

There has been a lot of discussion on this topic in the past few years, but I don't think there is an easy answer. I like to envision a future of scientific publishing that allows equal publishing opportunities for all scientists worldwide. In my opinion, several research-sharing platforms like bioRxiv have paved the way for sharing research quickly across the world. Achieving equal opportunity in publishing might potentially involve a lot of changes, such as implementing new methods to financially support publications, transparent peer review policies, offering recognition for peer review, encouraging more constructive criticism and requesting realistic experiments.

It's increasingly difficult to keep up with the huge volume of scientific literature. How much do you read and how do you choose what you read?

I am always looking for innovations in the area that I work on, but it is not easy to parse through the huge volume of literature. Even with the advent of newer paper sharing methods on social media, I still keep in touch with new papers via alerts and emails from journals and publication databases. I try to read papers in my area of research from all paradigms, ranging from in vitro analyses to simple model systems to studies of collective cell behaviours in the context of organismal development. I think this helps to give a more complete view of how a molecule functions across scales. I also learn about papers from journal club discussions with my students in the lab. I encourage students in my lab to attend conferences within India, and if possible across the world, as it is one of the best ways for us to learn about new research directly from the scientists conducting it.

What advice, on elements inside or outside the lab, would you give to scientists developing their careers?

Early-career scientists constantly have to deal with the pressures of teaching, publishing and grant writing but it is important to remember to just enjoy the process of discovery along with your students; I think that is one of the best things about this profession. I have found that some of the best moments in science are found in participating in discoveries made in the lab. When you celebrate these discoveries, I think it is also important to celebrate all the experiments along the way that led to a breakthrough: not only the ones that gave positive results but also the ones that gave negative results and helped shape the final story. Negative results can be really fun too, because they can shift the way you have been thinking about a question for a long time. We don't celebrate these experiences enough.

I would also advise anyone preparing to become a PI to take opportunities during your PhD and postdoc to work with undergraduate students by being a teaching assistant or participating in workshops and so on. This is invaluable training for learning how to work with younger, inexperienced students in the lab. I think it would be nice to make this a formal part of education as a graduate student or as a postdoc. When I became a new PI, one of my mentors immediately organised for a new student to join me. Just 2 days after I joined the Institute, she came to work in the lab! Learning how to mentor PhD students was a challenge. Every graduate student has a different set of requirements that they need from their PI, so I feel that we need to keep remoulding ourselves to connect and develop along with the student, which is hard at times. We're typically not formally educated on how to manage and mentor students, but over time I've realised that it's one of the nicest parts of being a PI.

Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

I like imaging cellular processes in development partly due to my interest in art and architecture! Seeing a result in the form of a beautiful microscopy picture satisfies both my hobby and my job-related interests. I also really enjoy making schematics about biological processes as we currently understand them. I think that if we can illustrate a process as a schematic diagram, then we can not only document it better but even come up with better ways of asking questions about what's happening in the process. I've told my colleagues that if I had enough free time, I would illustrate schematics for everybody! I would love to take a course on scientific illustration, illustration in general or animation.

Richa Rikhy was interviewed by Amelia Glazier, Features & Reviews Editor for Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.