Insight on Research

Repetitive peptides from the C9orf72 gene contribute to the most prevalent form of motor neurone disease, but it has been unclear how. Simon Bullock’s group help show how these peptides bind to both motor proteins and microtubule tracks to block neuronal transport.

The advent of brain organoid technology has enabled scientists to begin to ask what makes us human. Madeline Lancaster’s group has identified differences in early brain development that can help to explain the increased number of neurons in human brains over other apes.

Rare lipids in our cell membranes act as postcodes to operate regulatory processes such as autophagy and endocytosis. Roger Williams, together with Sean Munro’s and John Brigg’s groups, have shown how the G-proteins Rab1 and Rab5 activate these processes respectively, through conformational changes of kinase VPS34 complexes.

A powerful strategy to study protein function has been to deplete a protein of interest from the cell and then study the consequences. Leo James’ group has exploited new understanding of TRIM21’s mechanism of activation to develop new tools for targeted protein degradation.

Studying splicing fidelity has been difficult as some of the factors known to promote correct splice site use bind the spliceosome only transiently. Kiyoshi Nagai’s group have developed a method to study how proteins that ensure fidelity bind to RNA at different stages of splicing.

The intracellular immune receptor TRIM21 detects antibody-bound viruses inside our cells and targets them for destruction by creation of a polyubiquitin signal. David Neuhaus’ group, with Leo James’, has shown that TRIM21 is both the enzyme and recipient of the ubiquitination.