Inspirations : Manasi Bhate (UCSF) Deconstructing the Circuits of Life.

By Milka Kostic

      In addition to different research article types, Structure also publishes reviews on topics of high general interest for those using structural information to address difficult questions about biological function or to inspire new technology and solutions for human health. Why do we publish reviews? That’s an excellent question that deserves a post of its own. Suffice it to say that we think reviews enrich the scientific discussion by providing a deeper analysis and synthesis of existing knowledge at the time of writing.

People Behind the Structures is a Q&A section of our blog that introduces the authors of papers we published. We ask our authors to tell us more about their career paths, current research interests, and what they find inspiring. Today’s post is from Manasi Bhate from University of California, San Francisco, the first author of Signal Transduction in Histidine Kinases: Insights from New Structures, an exciting review that appears in the June 2015 issue of Structure.

ManasiBhate_0Manasi Bhate received an undergraduate degree in Chemistry and Biochemistry from Oberlin College in 2007. She also went on to Columbia University, where she worked with Ann McDermott and studied potassium channel structure and dynamics by solid-state NMR. She is currently a Jane Coffin Childs postdoctoral fellow in the laboratory of William DeGrado at UCSF, where she uses a combination of spectroscopy, biophysics, and protein design to study membrane proteins.


Milka Kostic: Tell us a little about your interest in structural biology. What motivated you to choose this field?

Manasi Bhate: I got into structural biology because of my interest in mechanistic biochemistry. I remember being blown away when I learned about the Krebs cycle and how it was deduced from a series of biochemical experiments on ground-up pigeon breasts.

I thought that, if one can figure out all of those mechanisms from indirect biochemistry, imagine what we could know if we could just look at all the various proteins in a cell. Structural biology lets you do just that—look at the system directly. Of course, structures don’t automatically tell you about a mechanism. In fact, they sometimes lead you down the wrong track, but a visual rendition of what might be going on is still a great starting point.

On a more practical note, I enjoy the everyday lifestyle that structural biology affords. Some days, I’m cloning proteins and doing biochemistry, some days I’m switching cables at the back of a spectrometer and optimizing pulse sequences, some days I’m programing and running computer simulations, some days I’m peering at structures – it’s never monotonous.

MK: What are your current research interests?

MB: I have a longstanding interest in cellular signal transduction and the principles by which protein structures encode and transmit information throughout the cell. Signalling is a dynamic process, and to understand it, we not only need to know about ensembles of protein structures and their dynamics, but we also need to figure out the spatial and temporal localization of signalling entities within the cell and then somehow integrate all the information. It’s fascinatingly complex!

More recently, I’ve also become interested in integrative approaches to solving protein structures, where you combine information from spectroscopy, biochemical experiments, and sequence analysis to build structural models of proteins. I think this has great potential for systems like membrane proteins that are often finicky and difficult to characterize using the standard structural arsenal.

MK: What are your plans for the future?

MB: I hope to start an independent research group in the next couple of years. I want to use bacteria as a model system for studying signalling and combining spectroscopic and biochemical methods to figure out how physical and chemical stimuli are turned into cellular information.

MK: Was there a particular mentor who helped guide you on your path?

MB: There’s more than one. I moved to the United States from India as a relatively clueless 17-year-old, and my undergraduate mentor, Manish Mehta, at Oberlin College really took me under his wing and helped me navigate the American system. When I moved to Columbia University, I was fortunate to have Ann McDermott as a mentor. She guided me through some fairly difficult times in graduate school with the thoughtfulness and wisdom that I can only hope to emulate some day. And here at UCSF, Bill DeGrado has been extremely supportive of my various ventures and is constantly motivating me to get out of my scientific comfort zone and try something new. So yes, I’ve been exceptionally fortunate with mentors.

MK: What are the main sources of inspiration for you, within the science or outside it?

MB: I find the history of science, particularly personal anecdotes and historical perspectives on biophysics, to be very inspiring. This field has such a rich history of terrific scientists with distinctive personal styles that really made an impact on society. Many of them lived and worked against all kinds of odds, often with less equipment and resources than we have today.

Max Perutz, for example, was locked away as an “enemy alien” and shipped off to an internment camp in Canada soon after he finished his PhD. There’s a great article he wrote for The New Yorker in which he describes his experiences and as a scientist in wartime England. When I read such stories and think about the impact that some of these people have had, I realize that I really have no business complaining.

MK: Which aspect of science, your field or in general, do you wish the general public knew more about?

MB: I wish there was a greater appreciation for basic science. I think most people easily appreciate the value of engineering or disease-related research, but much of the applied work relies on fundamental principles that come from basic science. If we want to continue to have new, impactful applications in 50 or 100 years, then we’ve got to support basic science today.

MK: Imagine that you had to pitch your research project to a panel of non-scientists using a tagline or a motto. What would your motto be?

Deconstructing the Circuits of Life.

Original Interview :