Research Fellows Directory
Dr Hirohide Takahashi
University of Cambridge
I am interested in the visualisation of biological molecules, especially those involved in vesicle budding and fusion. Mammalian cells contain many membrane-bound compartments. The compartments communicate with each other via vesicles, which bud from one compartment and fuse with another. These budding and fusion events are tightly controlled by specific sets of proteins. One budding step is carried out by a set of proteins called the endosomal-sorting complex required for transport (ESCRT) machinery. Intriguingly, the same complex is involved in the budding of some viruses, such as HIV, from infected cells, and also in cell division. Membrane fusion is mediated through so-called SNARE proteins. Fusion during neurotransmitter release is triggered by an influx of Ca2+ ions into the nerve terminal. The Ca2+ is detected by yet another protein, called synaptotagmin. The mechanisms underlying the operation of these groups of proteins are still poorly defined. My project aims to shed light on these mechanisms.
The method I am using is atomic force microscopy (AFM) imaging. AFM permits the study of proteins at nanometre resolution, and under the conditions that exist within the cell. So far, I have shown: (1) that the protein complex ESCRT-0 is able to cluster proteins bearing a molecular tag, known as ubiquitin; (2) that one of the SNARE proteins, synaptobrevin, forms ring-like structure that may be important in membrane fusion; and (3) that the two halves of the synaptotagmin molecule, known as C2 domains, interact together physically unless prevented from doing so by changes in the structure of the linker between them. These proteins are involved in key biological processes such as cell division, viral infection, and communication between nerve cells. When these processes go wrong the consequences for the organism, including man, are severe. I hope that by understanding how these proteins work I will be laying the foundations for future therapeutic advances.
Interests and expertise (Subject groups)