ICMCS Seminar - Force-probing biomolecular condensate

In the cell, biomolecules often function as part of large assemblies: membrane-less organelles assemble to compartmentalize the cell interior and coordinate metabolic pathways, viruses employ and induce intracellular condensates as a means to target specific cellular environments and to assemble new virus particles. Further, perturbed microphase separation is emerging as a key pathological mechanism in a spectrum of age-related neurodegenerative conditions. Thus, targeting phase-separated cellular compartments presents a promising new route to develop antivirals and drugs to treat neurodegenerative diseases.

In my talk, I will first present how we used atomic force microscopy and magnetic tweezers to characterize the formation, mechanics, and dynamics of sub-diffraction condensates involved in HIV replication. In addition, we show how a pre-clinical HIV inhibitor effectively impedes formation of an on-pathway condensation intermediate, but is inactive towards resolving the fully condensed state (Kolbeck et al., eLife 2024).

Next, I will discuss our current efforts to interrogate the physicochemical properties at the interphase of RNA-peptide condensates involved in familial amyotrophic lateral sclerosis. These condensate interphases are considered critical for their activation of the innate immune response, and present a first barrier towards condensate-resolving drugs. I will show how the liquid-like nature of the interphase renders high resolution probing by AFM problematic, yet feasible by mechanical and chemical modification the AFM probe.

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https://ed-ac-uk.zoom.us/j/81211470751

Meeting ID: 812 1147 0751
Passcode: Vk9c86c5