Leo trained with Prof. Dan Tawfik and Sir Greg Winter before establishing his own lab at the MRC Laboratory of Molecular Biology in Cambridge in 2007. 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 also led to the development of ‘TrimAway’, a technique which exploits TRIM21 for the rapid and specific degradation of cellular proteins.

The cytosolic Fc receptor TRIM21 uses antibodies to target proteins for degradation inside the cell. This activity provides potent immune protection by destroying incoming viral particles and exposing pathogen-associated molecular patterns (PAMPs) to innate immune sensors. When exploited as the technology “Trim-Away”, this protein degradation activity provides a rapid and effective alternative to genetic depletion/deletion approaches such as siRNA or CRISPR. In my talk I will discuss our recent work uncovering the molecular mechanism of cytosolic antibody-mediated degradation and how we are exploiting this mechanistic understanding to make new Trim-Away molecules and methods. I will describe how we have used Trim-Away degraders to remove tau aggregates in vivo in a mouse model of Alzheimer’s Disease.