Finding clarity within a blizzard- guiding the solution of cryo-EM structures

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Department
Biochemistry and Molecular Biology
Location
Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
Dr David Ascher david.ascher@unimelb.edu.au +61390354794 Personal web page

Project Details

The recent explosion in the power of cryo-electron microscopy has revolutionised the structural biology field, especially the characterisation of large protein complexes. This is helping us tackle very important biological problems in a way that they could never before. There are, however, inherent limitations that not only pose difficulties to the structure solving stage, i.e., properly positioning a protein chain within an electron density map, but also potentially introducing errors that might be propagated to the refined structure. This is especially relevant for medium resolution structures (4-8 Å). The problem is analogous to looking through blurry (or drunk) glasses and, without good points of reference, not being able to orientate yourself. To improve this procedure we can leverage the power of our existing structural and evolutionary knowledge accumulated over decades and deposited in structural databases in order to help guide the proposal of a more effective methods for this molecule placement. This project will use structural bioinformatics and machine learning to develop novel computational tools to aid cryo-EM and low resolution crystal structure solving, analysing protein residue environments, protein interaction interfaces, and protein functional sites. These methods will be brought together into an integrated platform for the evaluation and validation of medium resolution protein structures.



Faculty Research Themes

Cancer, Infection and Immunology



Research Opportunities

PhD, Masters by Research, Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Biochemistry and Molecular Biology

Research Group / Unit / Centre

Ascher laboratory: Structural biology and bioinformatics

Research Node

Bio21 Molecular Science and Biotechnology Institute

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