Lipid Leaders: Ayyalusamy Ramamoorthy

Tell us a little bit about yourself (current role, background, family, etc.)

Robert W. Parry Collegiate Professor of Chemistry and Biophysics, and Professor of Biomedical Engineering and Macromolecular Science & Engineering, at the University of Michigan, Ann Arbor.

Born in India, received PhD in Chemistry from the Indian Institute of Technology, Kanpur, India. Worked as a Scientist for JEOL Ltd., Tokyo, Japan.

Research Associate at Univ of Pennsylvania before joining the faculty of Michigan.

Family: married, and living with wife and 2 sons in Ann Arbor.

What do you consider the greatest breakthrough in lipid research in recent years?

Lipid nanodiscs and their applications are exciting. Lipidomics is also interesting. Since lipids play numerous roles in biology, investigating their biochemical and biological roles continue to be expanding and exciting. Roles of lipids in aging related diseases, gut-brain connection, and Alzheimer’s disease are particularly exciting.

Did you always envision yourself becoming a scientist? If not, what did you want to be when you grew up? Who influenced you to become a scientist?

No, I never thought that I would become a scientist and educator. Although my parents were farmers, I have been interested in studying from my childhood. My parents encouraged me to pursue education and supported me throughout my career. So, I am a first generation to go to college and to come out of the comfort zone to explore the academic & scientific worlds. I did not have long-term goals or dreams. But, I have always been interested in excelling whatever tasks that I undertook. So, I was fully focused on whatever I was doing whether it is a small or big task.

If I didn’t become a scientist, I do not know what I would have become. I was interested in music and also in sports; but I never had all the time required to become a professional musician or sportsman.

I was always inspired by my father, friends, and teachers to do better. The many challenges and difficulties that I faced in my career (and seeing others facing difficulties in their lives) motivated me to work hard and succeed. I also drew a lot of inspiration from successful persons in music and sports. Otherwise, there is no one influenced me to become a scientist.

What influenced you to become involved in the study of polymers for lipid-nanodiscs?

My research group has been working on developing membrane mimetics since joining the University of Michigan in 1996. Initially, we focused on developing and utilizing bicelles of various compositions. Then, we started to use protein (MSP) based nanodiscs, and later peptide-based and polymer-based nanodiscs. The interest in using nanodiscs was due to the need for “detergent-free” membrane mimetics to study membrane proteins such as cytochrome-P450. Once we started to use nanodiscs, students and post-doctoral fellows in the lab started to expand the tools. The challenges in studying membrane proteins and the difficulties faced by lab members in studying them collectively contributed to the development and applications of nanodiscs. So, I owe a lot to all the lab members and collaborators who have contributed significantly to these projects.

How might new, better polymer-based nanodiscs be able to further biophysical research?

Our research has not only developed novel polymers, it also demonstrated a variety of applications to study membrane proteins, protein-protein complexes, investigation of amyloid peptides, stabilizing small molecular compounds, enabling NMR applications, direct extraction of membrane proteins without the use of detergents, etc. I expect the polymer-based nanodiscs would dramatically expand the applications to study the structural biology of membrane proteins and their complexes (with ligands, proteins, DNA, or RNA), and to control protein aggregation, by a variety of biophysical techniques. They will also be used for drug/vaccine delivery, biological production and functional reconstitution of all possible membrane proteins, and for in-cell (and in-vivo) applications. There are a lot more basic physical and chemical research will also be emerging to create new avenues.

What are some of the advantages of the nanodiscs that your lab has created compared to other nanodiscs and detergent-based systems?

We have developed charged (positive or negative), neutral, and non-ionic synthetic polymers that form nanodiscs. We have demonstrated the size variability of nanodiscs, stability of nanodiscs against pH and divalent metal ions, functional reconstitution of oppositely-charged membrane protein-protein complexes in non-ionic polymer based nanodiscs, and the use of nanodiscs to control protein aggregation. We have also demonstrated the magnetic-alignment of nanodiscs for NMR applications and the ability to flip them in the NMR magnet.

What are your hobbies? What do you like to do outside of the lab?

Office work consumes most of my time even after at home. Writing and reviewing manuscripts and proposals, and reading publications effectively done at home. In the remaining time, I spend time with family. Taking my kids to different classes, playing with them, and watching TV/movies when they were small. Otherwise, my hobbies include listening to music, swimming, sailing (learning now), love to play ping-pong, and going out with family (love beaches and tropical places). I am also involved in helping those interested in education (especially the ones from poor background, and/or to enhance diversity). I also interact with friends to come up with educational activities (including international conferences and zoominar series) to serve the community.

Which Avanti products have you found particularly helpful with your research (if any)?

Amino acids and lipids labeled with isotopes (such as ¹⁵N, ¹³C, and/or ²H). Total lipid extracts from E.coli and neuronal cells. I will be interested in the synthetic polymers as well.