New DDLS Fellow: Andrea Fossati
Get to know DDLS Fellow Andrea Fossati (Karolinska Institutet) in our latest SciLifeLab & Wallenberg National Program for Data-Driven Life Science (DDLS) Q&A-style article. Andrea will be joining the DDLS Epidemiology and biology of infection research area.
Andrea studied in Italy for his undergrad and masters in Pharmaceutical Biotechnology. He obtained his PhD in Proteomics and Systems Biology working with Prof. Ruedi Aebersold at the Institute of Molecular System Biology (ETH Zurich), where he developed next-generation interaction proteomics approaches. As a postdoc with Prof. Nevan Krogan at the University of California, San Francisco, he studied virus-host interactions for prokaryotic and eukaryotic viruses using a combination of proteomics and functional genomics.
How do you think your expertise can contribute to the program?
My expertise is in mass-spectrometry based proteomics and specifically interactomics, which involves the study of protein-protein interactions. Throughout my PhD, I developed new methods for large-scale protein-protein interaction (PPI) profiling utilizing machine learning and deep learning.
Now, we can generate protein interaction networks that would take years to obtain with prior technologies within a week. This is particularly relevant for data-driven science because most proteins are organized in macromolecular assemblies (protein complexes), which represent key functional units regulating and catalyzing most cellular processes.
Despite viruses being the real ‘master manipulators’ of host PPIs, dysregulation of protein complexes has a profound effect on cellular states ranging from cancer to neurodegeneration. I think these approaches are particularly powerful as first-pass steps to investigate how a particular perturbation affects these networks and to rapidly generate hypotheses that can then be tested with traditional biochemistry or molecular biology methods.
Shortly describe your research in an easy to understand way.
Much like human cells, bacteria are susceptible to fatal viral infections. These bacterial viruses (bacteriophages, i.e phages) have gained significant attention in recent years as one of the most promising alternatives to antibiotics to tackle the emerging problem of drug-resistant bacteria.
However, just like our cells have immune systems aimed at eliminating viral infections, bacteria possess powerful phage defense systems which greatly reduce the efficacy of therapy using phages. Likewise, phages evolved mechanisms to escape these bacterial defenses resulting in the numerous anti-defense systems widespread across phage families.
Our lab’s main goal is to discover these bacterial defense systems, understand their composition and viral triggers as well as identifying phage mechanisms to evade them. Driving this goal is the desire to combat phage resistance mechanisms to make bacteria more susceptible to phage predation. In other words, we want to tilt the scale of the phage-bacterial warfare towards the phage by disabling the bacterial immunity.
How do you think the program and interactions with the other DDLS-Fellows will benefit you?
The DDLS program ticked all the boxes that I was looking for when applying for faculty positions as I am both a wet and dry lab biologist. Establishing a critical mass of data-driven researchers with a common interest in large-scale approaches will for sure lead to broad collaborations due to the general applicability of each fellow’s expertise. Being involved in data-driven life science education within the program and in Sweden is another reason that I am looking forward to joining the program.
Name one thing that people generally do not know about you.
I am an avid rock climber and backpacker.
Where do you see yourself in five years regarding the DDLS aspect?
Over the last five years the field of bacterial immune systems exploded with hundreds of new systems discovered.
Understanding which bacterial genes restrict phage replication could be used to design small molecules to ‘immunosuppress’ bacteria and boost efficiency of a phage therapeutic. Overall, these are long term goals but providing a blueprint of the bacterial immunity at the systems level is the first critical step for later translation.
These findings, and the general experimental and computational approaches we will develop in the next 5 years, may have broad utility and impact beyond host-phage interactions as some of these systems do closely resemble human ones.
The recent discovery of a human CRISPR like protein complex shows that there might something to learn about basic human immunology by studying bacterial immunity and our collaborations with DDLS fellows and Swedish researchers with complementary expertise will be a key component of this endeavor.
In one word, describe how you feel about becoming a DDLS-Fellow.
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