The Institut Pasteur–UCSF QBI "Faculty Mini-Sabbatical Program" is designed to exchange top academic talents from the Institut Pasteur and the University of California San Francisco for one- to three-month visits to build knowledge and new partnerships. The purpose of sabbatical leave is to provide an opportunity for faculty members to engage in scholarly, creative, professional, research, or other academic activities that will enhance the faculty member's further contributions to their institution and the world in the name of scientific research and excellence towards pandemic preparedness. In this sense, the visiting scientists will get the opportunity to interact with leading scientists from either institution on their research programs. 

Marc Lavigne, Research Director at the Institut Pasteur, provides a reflection of his time at UCSF as part of the Mini Sabbatical Program. 

What is the focus of your research?

Our research projects are focused on nucleic acid/protein complexes playing a role during the replication of highly pathogenic human viruses. Recently, we have focused our studies on non-canonical nucleic acid structures called guanine quadruplexes (G4), which regulate HIV-1 genome expression and SARS-CoV-2 replication. Our goals are to characterize the mechanisms and partners of these regulations. We mainly perform fundamental research based on in vitro approaches, but we have also initiated translational studies on G4 ligands targeting HIV-1 latent copies or SARS-CoV-2 Nsp3 interacting RNAs.

How does your work keep you motivated?

For a long time, I have been working on HIV-1 and I think it is still crucial to study this virus. Present anti-HIV therapies, although very efficient, don’t eliminate completely this virus in the persons living with it and we need to find new strategies to purge the cellular reservoirs containing latent integrated viral copies.

On coronaviruses, our efforts to study these viruses need to be continued, to provide a better knowledge on their replication mechanisms that will be crucial in the event of an outbreak of infection by highly pathogenic strains.

Finaly, I am always fascinated by viruses and the diversity of replication mechanisms. They frequently divert or mimic cellular pathways, and studies on their replication cycles allow to discover new cellular mechanisms.

Which labs are you collaborating with during this mini sabbatical and how do your visions synergize?

During my sabbatical, I have been hosted by Geeta Narlikar who is a recognized expert on the mechanisms of nucleosome remodeling and chromatin folding. Recent studies performed by her laboratory have revealed a new property of HP1 proteins, based on their property to phase separate in vitro and in cells. The goal of my sabbatical has been to evaluate the properties of G4s to regulate phase separation of G4 binding proteins, but also to learn the methodological methods developed to investigate the mechanisms and partners associated with this process. Promising results have been obtained and we intend to continue this fruitful collaboration. During this sabbatical, I have also discussed with several PI of the UCSF and the Gladstone Institute. I wish these discussions will contribute to initiate collaborations on different projects related to chromatin folding and antiviral screening.

Why is it important to you to connect with scientists across the globe? Why is it so valuable to interact in person?

My team is small, and its research activities rely on collaborative work. To study HIV and SARS-CoV-2, we have established interdisciplinary consortia gathering complementary expertise in chemistry, biophysics, biochemistry, cellular biology and virology. Our present collaborations are mainly with French laboratories, and we would like to extend our collaborative network to other countries, especially within the USA, characterized by its huge scientific research activity. Conversely, it is also important for me to establish contacts with lower budgets countries to be involved in their research development. This is one of the challenges of the Pasteur Network, which is an alliance of 32 institutes spanning 25 countries across 5 continents, fostering a dynamic and diverse community of knowledge and expertise.

How do you intend to maintain the connections you have made during your stay?

I will continue to discuss with Geeta and exchange ideas, expertise and material with her. We also intend to apply for collaborative fundings, which are crucial to establish our starting collaboration. We wish our collaborative work will reinforce the links between the QBI-UCSF and the Institut Pasteur.