Trim-Away: Targeted degradation of pathogens and proteins

Key Facts

Speaker: Dr. Leo James
Employer and Department:
MRC LMB
Location:
MSI-SLT
Date and Time:
Thu 10th Nov 2022 - 13:00

Abstract:

Antibodies can target intracellular proteins for degradation by recruiting the cytosolic Fc receptor and E3 ubiquitin ligase TRIM21. This activity provides potent immune protection against viral infection and is also effective against proteopathic agents like tau. When exploited as the technology “Trim-Away”, the resulting protein depletion provides a rapid and effective alternative to genetic depletion/deletion approaches such as siRNA or CRISPR.  In my talk I will discuss how we are developing Trim-Away further and describe a new role for TRIM21 in antigen presentation, where it may participate in protective T cell responses against enveloped virus infection. Finally, I will present data on a second TRIM family protein that is also capable of degrading pathogens and proteins.

Bio:

Leo received his Ph.D. from Cambridge University in 2000 and post-doc’d with Prof. Dan Tawfik and Sir Greg Winter, on antibody structure, function and evolution. Leo leads a research group at the MRC Laboratory of Molecular Biology in Cambridge, which investigates virus-host interactions using a broad range of in vitro and in vivo techniques. Significant work includes the discovery of the cytosolic antibody receptor TRIM21 and dissection of how it prevents infection by intercepting viruses, bacteria and pathogenic proteins inside the cell and targeting them for rapid degradation. This work has also led to the development of ‘TrimAway’, a technique which exploits TRIM21 for the rapid and specific degradation of cellular proteins. Leo’s lab also investigates HIV infection; recent work includes the discovery that HIV uses dynamic pores in its capsid to import nucleotides for DNA synthesis and HIVs exploitation of cellular metabolite IP6 to build and stabilise these structures.