Reflecting on the journey so far and embarking on a research career

Hello!

This is Rupesh with another blog post to provide an update on what happened during and after my traineeship. You can find my previous post here. It took me a little longer to write this post than promised, but here we are!

Let me start with a short recap: For the traineeship, I worked on my MSc thesis under the supervision of Dr. Ilona Rissanen and Prof. Juha Huiskonen at the Institute of Biotechnology in the University of Helsinki. My thesis was on a project aimed at discovering the structural basis of SARS-CoV-2 neutralization by the antigen-binding fragment of an antibody that was derived from a COVID-19 patient. We can understand how the antibody manages to neutralize the SARS-CoV-2 virus by figuring out where it binds to the spike protein. The antigen-binding fragment, as the name suggests, is the part of an antibody that recognizes and binds to the antigen. In order to find out the epitope of the antigen-binding fragment, I employed single-particle cryogenic electron microscopy (cryoEM). I was able to hypothesize the neutralization mechanism based on the location of the epitope and the subsequent analyses of it.

During the traineeship, I got to learn some cool techniques involved in studying a protein through cryoEM, right from sample preparation to processing the collected data. I would like to highlight a moment during my thesis work, when I got to see how the spike protein looked like in 2D in the early stages of processing the data. It was stunning to see the proteins I had expressed on the computer screen!

But the main takeaways, in my opinion, were the discussions I had with my supervisors and other lab members on how to troubleshoot experiments and interpret the results. That was where I got to understand how to approach science and the problems that arise in these projects. I found these discussions, both formal and informal, to be highly beneficial to my development as a researcher. Writing my thesis was another area where I found myself constantly learning and applying the knowledge to put the big picture together. It involved reading a lot of research articles, which was not an easy task but once I got into the thick of it, I was surprised to notice how fulfilling it was. Staying on top of current research in the field does feel good.

My thesis work had come to an end right after the traineeship period ended and it was time to submit my thesis before the academic year came to a close. As part of graduation requirements, the Genetics and Molecular Biosciences (GMB) master’s program provides the opportunity to present our thesis work during the annual GMB master’s thesis symposium. It was the first time I got to be a part of an in-person symposium in a very long time. In fact, it was the first time I got to see most of my fellow students in the program. All of us presented our work with great enthusiasm and held passionate discussions. It was a good experience to present my results to an audience with varied background and to also listen to talks on different lines of research that my colleagues were working on.

I graduated from the GMB master’s program a couple of months ago and I am incredibly thankful for having the opportunity to work in the research groups of Dr. Rissanen and Prof. Huiskonen. A huge thanks to HiLIFE for supporting me during my thesis. The traineeship resulted in a series of wonderful events which would go on to help me build myself as a researcher and for this, I am grateful!

As for the present, I have recently started to work as a research assistant with the same research groups where I’m hoping to enrich my skills even further before I embark on the journey towards a PhD next year. I’m cherishing this phase of my life where I get to do cool science surrounded by an awesome community, long may it continue!

Cheers,

Rupesh

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