The goal of Gang Dong’s ‘CytoPocket’ project is to uncover how Trypanosoma brucei – the parasite responsible for the African sleeping sickness – uses its unique flagellar pocket to evade the immune system, focusing on the poorly understood interface between the cytoskeleton and the membrane. Central to this effort is characterizing the filament-forming properties of a key structural protein, BILBO1, and identifying additional membrane proteins that regulate the formation and function of this essential cellular gateway. Gang explains: “Our goal is to turn the flagellar pocket from a biological ‘black box’ into a fully defined molecular machine.” By integrating X-ray crystallography, cryo-EM, and an innovative minimal cell system to visualize parasite proteins with unprecedented clarity, the project aims to reveal how this intricate machinery is built – and where its vulnerabilities lie. Conducted in collaboration with two research groups at the University of Bordeaux, ‘CytoPocket’ is set to generate fundamental insights into parasite cell biology and pave the way for future therapeutic strategies against sleeping sickness.
Javier Martinez’s project explores an emerging connection between oxidative protein degradation and the tRNA ligase complex (tRNA-LC), a key enzymatic machinery responsible for re-ligating tRNA halves after intron removal. Building on a recent breakthrough describing a novel oxidation-based pathway for protein turnover, the Martinez lab aims to uncover how this mechanism targets and dismantles the tRNA-LC – an unexpected link that implies an entirely new layer of regulation in RNA biology. “We knew many things about the tRNA-LC, but we had no idea it could be specifically degraded by an oxidative mechanism”, Javier explains. His team will investigate which component of the five-protein complex is initially targeted, where degradation occurs within the cell, and how accessory factors contribute to the process. The project will also explore the potential involvement of the PAM enzyme in the process and develop oxidation-resistant variants of the tRNA-LC. The project brings together collaborators from the ETH Zürich, the Max Planck Institute in Dresden, the Charles University in Prague, and the University of Nova Lisboa.