We are excited to offer a PhD studentship to study protein ubiquitylation and deubiquitylating (DUB) enzymes. The project will be conducted at the University of Leeds, which offers a vibrant research environment and state-of-the art infrastructure for structural and molecular biology, biophysics, cellular imaging and proteomics.
Ubiquitination of proteins serves as a post-translational signal to regulate virtually all aspects of cellular life through the precise spatial and temporal control of protein stability, activity or localization. Maintaining the right balance between ubiquitination by ubiquitin ligases and deubiquitination by DUB enzymes is crucial, since deregulation of cell signaling networks governed by ubiquitin can lead to disease. DUB enzymes and their regulators are frequently mutated in cancer, neurodegeneration, inflammation and other human diseases.
Recent studies at preclinical and clinical levels have implicated ubiquitin signalling pathways as bona fide targets for cancer chemotherapy. The ubiquitin system with its numerous enzymatic components represents a rich and currently untapped area for the development of new therapeutic disease targets.
In this project, we will study the structure of DUBs that function as large multi-subunit complexes and identify their cellular functions. Studying these large molecular machines by advanced methods of structural biology represents an exciting opportunity to uncover additional mechanisms of DUB regulation. To delineate function, we will use a combination of genetics, biochemistry and molecular biology approaches in Drosophila melanogaster both in vivo and tissue culture.
The project will be conducted at the Astbury Centre for Structural & Molecular Biology at the University of Leeds. The Astbury centre offers a vibrant research environment and state-of-the-art infrastructure for cryo-EM and X-ray crystallography.
The studentship offers a unique opportunity to experience research and to receive training in a variety of advanced modern techniques in structural biology, biophysics, Drosophila genetics, cellular imaging and tissue culture.
Techniques you will learn and use:
- Cryo-electron microscopy and X-ray crystallography for determining structures of proteins and protein-protein complexes
- Drosophila genetics and phenotypic assessments
- Biophysical techniques such as fluorescence polarisation and calorimetry
- Use of MultiBac for large-scale production of multiprotein complexes in insect cells
- Cell biology and cellular imaging assays
- Tissue culture and molecular biology
In addition to training in a broad range of molecular laboratory techniques, the studentship will provide access to a diverse range of additional training opportunities aimed at supporting the progression of the PhD and developing transferable skills.
Experience in structural biology is not required and suitable training will be provided.
Further information about research in the Zeqiraj and Aspden laboratories can be found via the links below.
Zeqiraj lab: http://www.personal.leeds.ac.uk/~fbsez
Aspden lab: https://aspdenlab.weebly.com/
Informal enquires can be made to Dr Elton Zeqiraj ([email protected]
) or Dr Julie Aspden ([email protected]