A journey to understand SARS-CoV-2 neutralization through cryoEM

Hello!

My name is Rupesh, and I’m a second-year master’s student studying in the Biochemistry and Structural Biology study track of the Genetics and Molecular Biosciences program at the University of Helsinki. I come from Chennai, a beautiful city in the south of India. I did my Bachelor’s in Biotechnology in Chennai and graduated with an engineering degree, B.Tech. For as long as I can remember, I have been drawn towards Molecular Biology and Biochemistry. And so, for my bachelor’s thesis, I worked in a virology lab at the CSIR – Centre for Cellular and Molecular Biology in Hyderabad, India. I thoroughly enjoyed my time there and developed an appetite for research, in viruses and molecular biology to be precise.

I started my master’s studies at the University of Helsinki in 2020, and in the very first semester, there was this one course which I really liked: GMB–105 Introduction to structural biology and biophysics. Being a part of that course felt refreshing and I still remember saying to myself, ‘When I have to search for labs to do my master’s thesis, I am going to ask the structural biology labs first’. And that is exactly what I did a few months back. I reached out to Dr. Ilona Rissanen and Prof. Juha Huiskonen who are working on structural virology and structural biology of macromolecules and interactions respectively. It was a fruitful attempt, as I got the opportunity to work on a short-term research project on the development of protein scaffolds for cryogenic electron microscopy (cryoEM) under their supervision at the Institute of Biotechnology.

Currently, I have just started working on my master’s thesis project, happily continuing under their supervision. My project is aimed at discovering the structural basis of SARS-CoV-2 neutralization by an antigen-binding fragment (Fab) from a patient-derived monoclonal antibody that targets the spike protein. I will use single-particle cryoEM to elucidate the molecular architecture of the Fab-bound spike protein trimer and identify the epitope of the Fab. The project benefits from a thriving collaboration with the iCoin consortium, funded by the Academy of Finland, which aims to isolate SARS-CoV-2 neutralizing antibodies from Finnish COVID-19 patients to further the research on virus inhibition by the humoral immune response.

I could not have asked for a better environment to guide me in carrying out this project. I got familiar with some of the techniques and protocols that will be used in my thesis during my short-term project. I hope to build on those skills and hone them even further, especially in making and handling grids for cryoEM.

I’m honored to have been chosen as a HiLIFE research trainee. The research standards are set incredibly high at the University of Helsinki, which makes this traineeship even more prestigious. With the support from HiLIFE, I believe I can do amazing science, learning from the experts. Hopefully, this is the beginning of an exciting journey in research!

I will be back later this spring to share some exciting results with you. Until then, take care!

Rupesh