Visualizing Filamentous Actin Using Synthetic Biology and Click Chemistry

Project:
Fundamental to the organization of cell morphology and form in all cells ranging from bacteria to human is its skeleton (termed the cytoskeleton). A number of cytoskeletal systems have been described, a very important one being the actin cytoskeleton, which is well known for its role in muscle contraction and cancer metastasis. One of the best ways to investigate the cytoskeleton and how it promotes cell function (in processes such as cell division, cell migration etc.) is to visualize it using advanced microscopic tools, which can enable us to see biological molecules even a millionth of a millimetre in size. However, the key protein that makes up the actin cytoskeleton, actin (which forms polymeric tracks), is difficult to label with light bulbs (fluorescent tags) that will enable its visualization in microscopy. We plan to make a step change in the detection and imaging of the actin cytoskeleton using synthetic biology approaches in which we will introduce ultra small handles in the form of unnatural amino acids into actin. These handles will be hooked onto fluorescent molecules through organic chemistry approaches. Light bulbs will be introduced at a number of locations in actin, one at a time, and the ones that do not perturb function of actin will be used in advanced imaging experiments. Once the methodology is established, the student will investigate many aspects of actin behaviour in vitro (in a test tube, through purification of the actin protein that was made in cells) and in vivo (in living organisms using advanced microscopic techniques). These studies should provide major insight into basic biology as well as diseases such as cancer metastasis, cardiovascular disorders, and more.

Programme overview:
This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.