Over the course of evolution viruses have perfected the art of repurposing their host’s cells for their own survival. They hijack the transcriptional or the translational machinery of cells to replicate their own genetic information and remodel signaling pathways, all while evading the host’s immune system. The lab of Marco Hein will use CRISPR/Cas9 based genetic perturbations, single cell transcriptomics, and proteomics to study the principles of virus-host interactions.

 

Marco, you are trying to obtain a comprehensive understanding of what happens to a cell when it gets infected with a virus. What is unique about your approach, and what advantages does it have compared to more traditional virology or immunology?

All the work that I do is based on decades of research in virology, immunology, and cell biology. I think that I can add to this with a genome-wide or proteome-wide perspective because you are not biased by proteins you already know or that you have a scientific intuition about. I think this will help us to make observations that no one had on their radar before.

What do you hope to accomplish in the next 10 years with your group?

The big picture of what my lab is going to do is develop technologies to understand the interactions of viruses with their hosts. I plan to develop technologies that are scalable, so I can do this one virus at a time and not one viral gene or one protein at a time.

What motivates you to achieve these goals?

This moment of excitement when you find something new, which is quite rare, but extremely satisfying. I think that's one of the most rewarding things you can experience. The moment when you feel that your trainees have made progress and have really grown as scientists is also very rewarding.

In your PhD thesis, you used proteomics to map the human interactome, which explains your interest in systems biology. How did you then get interested in virus-host interactions?

This is really serendipitous. When I started my postdoc in San Francisco, my advisor pitched an idea to me. This was in the early days of CRISPR screening, which was a fairly new technique at the time. He suggested to use CRISPR Cas9 to target not human genes, but the genes of a virus that has a DNA genome just like us. Since then, this idea of working in a host-pathogen system has really fascinated me.

You still use proteomics in your research. Why is it such an important method in your work?

Proteomics is the method of choice if you want to study and characterize all the proteins that are in a biological sample, and not only identify them, but also quantify them. And in that sense, it's a really fundamental technique that you can plug into many biochemical workflows and use as your ultimate readout. During my PhD that readout was protein interactions. Now, I plan to use it to study the change in the composition of organelles in infected cells.

Viruses are millions of years old and their evolutionary origins are still shrouded in mystery. What fascinates you about viruses?

They are very small entities, yet they have immense disruptive power. They enter a host cell with minimal genetic information but have the power to completely take over an infected cell, hijacking its pathways, reorganizing its architecture and turning it into a viral factory. I am fascinated by the idea that they reprogram our own cellular pathways for their own benefits. Studying that reprogramming really helps us learn more about the functions of our cells, because viruses have perfected how to hijack those functions over the course of evolution.

Arguably the most infamous virus in recent years is SARS CoV-2. What do you think is the biggest learning from this pandemic?

Scientifically, the pandemic really underlined the importance of funding basic research. I think many of the purely scientific developments, such as antivirals, but most importantly the mRNA vaccines, are really a triumph of basic science. For decades people have funded research in rather obscure areas, which has now come to fruition. At the same time, the pandemic also underlines the importance of human psychology, which many scientists maybe didn't have on their radar. It’s not only important to do the science, but also to communicate your findings, both to the public and to policy makers in a way that is approachable to them and not too abstract. There is a need to translate the information into actionable things that we as a society need to do.