First person – Priyanka Kothari

Priyanka Kothari

How would you explain the main findings of your paper in lay terms?

Cells have the amazing ability to sense and quickly respond to the chemical and mechanical signals they experience. There are many moving parts that are responsible for these responses, and we were interested in how those parts fit together to allow the cell to mount a response. Imagine constructing IKEA furniture, with numerous pieces that have to be assembled correctly to form a functional piece. Just as IKEA categorizes and packages certain components together to aid the assembly process, we have found that cells form ‘packages’ of key components in the cytoplasm to ensure its ability to mount a quick, robust response upon recognition of a chemical or mechanical stimulus. Proteins that are important for generating contractility in the cell, including non-muscle myosin II, the actin cross-linker cortexillin I, and the scaffolding protein IQGAP2 form ‘contractility kits’, and the negative regulator of contractility IQGAP1 prevents the formation of the kits.

Another key concept we reveal is that there is feedback between seemingly diverse processes in the cell, such as metabolism, transcription and translation, and cell mechanics. By deciphering the key interactions between these components, we are uncovering new biology that will help us further understand how the cell senses and responds to its changing environment.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Making sense of the complicated network of protein interactions was definitely a challenge with this project. We streamlined the interactors that were discovered through the mass spectrometry effort by comparing the hits to lists of proteins that were previously implicated as interactors with the contractility network. By fluorescence cross-correlation spectroscopy (FCCS), we detected changes in protein–protein interactions in different genetic backgrounds. Compiling the in vivo K_D values on a single map helped us visualize all of the interactions together to start to decipher the complexity of the mechanobiome.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

Compiling our analysis of the single molecule pull-down (SiMPull) experiments with cortexillin I and IQGAP1 was a particularly exciting moment. Discovering that two molecules of IQGAP1 complexed with a cortexillin I dimer was a critical piece of the puzzle that helped us reveal the mechanism of how IQGAP1 inhibits the myosin II-cortexillin I contractility kits. It was particularly exciting to have this result come from the collaboration with Vasudha Aggarwal in Taekjip Ha's lab, as we were applying this single-molecule approach to Dictyostelium for the first time.

Why did you choose Journal of Cell Science for your paper?

Journal of Cell Science is a premier cell biology journal that makes high quality, fundamental research accessible to the scientific community. In addition, the journal has been making great efforts to support the development of early-career scientists through its First Person and Cell Scientist to Watch sections. The preLights preprint highlight service is another example of the journal's support for leading the growth of the scientific community. Journal of Cell Science is a wonderful example of a journal run by biologists for biologists.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

Incredible mentors have encouraged me to pursue a career in science. Mr Coe was an enthusiastic, passionate teacher who initially sparked my curiosity in biology in middle school. During my undergraduate career at Penn, I worked in Dr Michael Lampson's lab where I first learned the power of integrating biology with physics. Since then, I have been fascinated with how cells respond to mechanical forces, which is why I was excited to join Dr Douglas Robinson's lab for my PhD at Hopkins.

Who are your role models in science? Why?

Over the course of my training, I've had a number of important scientific mentors and role models. However, the ones that stand out the most to me are the individuals who mentored me not only in science, but in the power that science can have on the community. Dr Alexandra Surcel, a research associate in the Robinson lab, and my graduate advisor, Dr Douglas Robinson, have been instrumental in not only showing me the disparities in education and support for historically marginalized individuals, but also how we as scientists can make a difference in their lives. They have led by example and proven that one can be an incredible scientist and build programs that benefit the community at the same time. To me, they epitomize the achievement and widespread impact that is the responsibility of all scientists to strive to achieve. I plan on taking these lessons and skills to continue science outreach and I hope to one day have the opportunity to set the same example for my mentees.

What's next for you?

I am extremely excited about the opportunity to use the skills I have learned during grad school to help deliver a drug through the discovery and development pipeline.

I am currently working on a few other projects in my PhD lab before I graduate, but I aim to enter the biotech industry as a scientist. I am extremely excited about the opportunity to use the skills I have learned during grad school to help deliver a drug through the discovery and development pipeline. One thing that draws me to biotech is that individuals from entirely different backgrounds and functions (biological discovery, pharmacology, analytical chemistry and manufacturing) work as a team to develop a drug to positively impact patients' lives.

Tell us something interesting about yourself that wouldn't be on your CV

I am trained in Kathak, a classical Indian dance style. I have always found music and dance powerful ways to tell stories, and I love the energy and positivity they bring.