One of the grand challenges of structural biology is to produce molecular level understanding of cells, tissues and even entire organisms. Towards this goal, we would like to decipher structures and locations of all macromolecules in human tissue infected with pathogenic bacteria using electron cryotomography (cryo-ET) / subtomogram averaging, combined with mass spectrometry performed in a novel instrument with bespoke hardware.
We are looking for an ambitious student who would like to learn in situ cryo-ET to produce atomic structures from infected tissue. While cryo-ET can provide pictures of specimens at high spatial resolution, different macromolecules cannot be easily distinguished from each other in black and white microscopy images. To circumvent this problem; mass spectrometry (MS) is a structural biology technique that allows the exact chemical identity of molecules in a sample to be determined. The second part of this project to study the molecular landscape of infected tissue will combine EM and MS imaging to accurately identify molecules inside cells. Combining high-resolution structures solved directly from tissue (or tissue-like specimens) with spatial MS data will be used to decipher a high-resolution snapshot of a cell.
This proposed project represents basic research, using the latest hardware and software advances in cryo-ET and MS. These latest developments (all already running in our lab) will be applied to important biological specimens for obtaining unique physiological insights into phenomena at the cellular and tissue level. This project is ideal for a student interested in microscopy, with an indomitable spirit of exploring uncharted waters. More details will be provided during the interviews.
There is flexibility in the exact biological direction of the project depending on the interests and expertise of the ideal student. Broadly, we are studying how surface molecules in bacterial pathogens shape human infection. There will be opportunities within the project to learn focused ion beam milling of tissues, electron tomography (cryo-ET) and advanced data analysis techniques including subtomogram averaging structure determination from cells.
Our laboratory is friendly and highly collaborative, with details of the research projects almost always arising from brainstorming sessions and lively discussion between lab members and other members of the LMB. There is ample support in our lab and at the LMB for microscopy, image processing, MS and bioinformatics directly available to the candidate. We welcome applications from students of all scientific backgrounds.