New Voices in Infection Biology
New MPIIB virtual seminar series | Kick-off with Enfu Hui
The MPIIB is returning to the lab to start experiments. While it's exciting to do science again, there is one aspect still missing in these times: a lively and interactive seminar series. To stay connected in these times of social distancing and create a platform where we can learn about new science happening across the world, we are launching a virtual seminar series.
This seminar series will focus on early career researchers. We aim to give early career researchers working in infection biology visibility and a platform that they can communicate their work (and we get to hear about their awesome science!).
In the coming weeks, we will be updating you on seminars that you can stream live. We invite the world to listen and learn with us! While we may be social distancing, we want to take this opportunity to build bridges with other scientists across the globe!
If you are interested in joining the seminar, please contact: firstname.lastname@example.org
Once registered, you will receive a zoom conference link 30 mins before the talk starts - please sign in using your full name.
Enfu HuiUniversity of California, San Diego, USAMax 13, 4 pm (CEST)Talk abstract:
Immune checkpoints PD-1, CTLA-4 and BTLA act as critical brakes to prevent autoimmunity, but can also be hijacked by tumors to escape destructive immunity. Molecular understanding of these molecules has lagged behind the clinical development of their inhibitors. My lab studies the mechanism and regulation of immune checkpoints, using a combination of biophysical, cell biological and immunological approaches. In this upcoming seminar, I will discuss our recent findings concerning a novel mechanism of PD-1/CTLA-4 crosstalk and mechanistic disparities of PD-1/BTLA.
Washington University, St Louis, USA
Wednesday, May 20, 4 pm CEST - Berlin
Following the infection of a cell, individual particles from some RNA viruses are capable of producing large numbers of extremely diverse progeny. These progeny can vary widely in their genetic sequence as well as in their structural and molecular characteristics. Influenza A virus (IAV) is a famous example: in addition to their genetic diversity, clinical isolates of IAV adopt a filamentous morphology where particles can vary in length by over 100-fold. While the importance of genetic diversity in viral persistence and adaptation is well-established, the role of phenotypic heterogeneity – differences in the size, shape, and molecular composition of virus particles that may be otherwise genetically identical – remains unclear. Are some particles more likely than others to infect a cell, become neutralized, or activate an immune response? To address these questions and connect the characteristics of individual virus particles to functional outcomes, we use a combination of fluorescence microscopy and site-specific labeling of engineered viral strains to study viral infections at the single-particle level. In this talk, I will describe our efforts using these tools to understand how phenotypic heterogeneity in evolutionarily divergent human respiratory viruses contributes to aspects of virus replication and transmission.
Hawa Racine Thiam
National Institutes of Health | NIH · National Heart, Lung and Blood Institute (NHLBI)
May 27, 3 pm (CEST)
Neutrophil extracellular traps (NETs) are web-like DNA structures decorated with histones and cytotoxic proteins released by activated neutrophils. Initially described as a way for neutrophils to trap and neutralize pathogens during innate immunity, NETs are now widely implicated in the detrimental effect of several autoimmune diseases. Peptidylarginine deiminase 4 (PAD4) citrullinates histones and is required for NETs formation (NETosis) in mouse neutrophils. While various molecular mechanisms mediating NETosis are being revealed, the cellular events driving NETs release are still unclear. Here, we determined the sequence of cellular events in NETosis, and examined the role of PAD4 in these events. We performed high resolution time-lapse microscopy of mouse and human neutrophils (PMN) and differentiated HL60 neutrophil-like cells (dHL-60) labelled with fluorescent markers of the cytoskeleton and organelles and stimulated with ionomycin, lipopolysaccharides or C. albicans to induce NETosis. We found that stimulated neutrophils eject extracellular DNA after decondensation of the nuclear DNA in the nucleus, rupture of the lamin meshwork and nuclear membrane allowing the release of decondensed chromatin to the cytosol, disassembly of the actin, microtubule and vimentin intermediate filaments networks, vesiculation of the endoplasmic reticulum and plasma membrane and finally rupture of the plasma membrane. More importantly, we found that these cellular pathways occur in a specific and well conserved temporal order suggesting a requirement for a precise sequence for progression through NETosis. Indeed, inhibition of actin disassembly, one of the first cellular events, blocked NET release. To examine the role of PAD4 in NETosis we isolated neutrophils from PAD4-deficient mice and generated a PAD4-knock down (KD) HL60 CRISPR line. We found that chromatin de-condensation, lamin meshwork and NE rupture and extracellular DNA release required the enzymatic and nuclear localization activities of PAD4. Thus, NETosis proceeds by a step-wise and well conserved sequence of cellular events culminating in the PAD4-mediated expulsion of DNA. Our data further suggest that targeting these cellular pathways might be a better approach for controlling NETosis progression than targeting the various divergent signaling pathways.