Dr. Timo Oosenbrug

Research:

Unravelling mechanisms that control antiviral Toll-like receptor signaling in time and space

Host defence against infection critically depends on the innate immune system, wherein invading pathogens are sensed by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are PRRs that have emerged as key sensors to microbes, for example recognizing components of DNA viruses such as nucleic acids and envelope glycoproteins.

The output of TLR stimulation is dictated by a variety of factors, including the receptors’ subcellular localization. Inadequate trafficking of TLRs or their ligands is implicated in recurrent viral infections and autoimmune diseases, highlighting the importance of activating TLRs at the right time and location. Yet, factors and pathways governing the spatiotemporal organization of TLR signaling remain largely enigmatic.

In my project, we combine microscopy and biochemical experiments with chemical immunology in a multidisciplinary approach, to identify cellular factors and pathways that regulate TLR signaling in “time and space” in human cells. Subsequently, I intend to investigate how these cellular processes contribute to shaping antiviral immune responses of appropriate quality (specificity, amplitude and duration).

Curriculum Vitae:

I studied Life Science & Technology at the Technical University Delft and Leiden University, the Netherlands. My master’s research project was performed at the VSB section of CCB, under supervision of Maaike Ressing. During this project, we focused on a lytic gene product of the Epstein-Barr virus that lowers surface levels of the lipid antigen presenting molecule CD1d. This may represent an immune evasion strategy to withstand activation of CD1d-restricted iNKT cells. In 2016 continued as a PhD student in the same group, working on a new project on Toll-like receptor signaling. For this project, I received a grant from the Infection, Immunity, and Tolerance NWO Graduate programme.