A PhD position is available in the group of Cyril Dominguez at the University of Leicester.
The successful candidate will work in the Molecular characterization of Sam68-driven cytoskeletal reorganization.
The application deadline if Friday the 11th of March.
Information on the project and how to apply can be found at:
The cytoskeleton is a complex network of various fibres (microtubules, actin, …) that is essential for cells to maintain their shape and internal organization and for their migration. It is a very dynamic network that reorganize constantly especially during the cell cycle. Like most essential processes, the cytoskeleton organization is highly regulated by regulatory proteins and its misregulation is a hallmark of cancer cells invasion and metastasis. the molecular processes underlying such changes in both normal and disease states are still poorly understood and require further investigation.
Sam68 is an oncogenic RNA-binding protein whose increased _expression_ is correlated with poor prognosis in multiple cancers such as prostate and colon cancers. Sam68 display multiple functions in the cell. Its best characterized function occurs in the cell nucleus and is the regulation of alternative splicing, a process that allow cells to produce multiple proteins from a single gene. However, Sam68 is also localized in the cell cytoplasm but its cytoplasmic functions remain largely unknown. It has been suggested that Sam68 plays a role in cytoskeleton reorganization since depletion of Sam68 leads to defects in cytoskeleton organization in cancer cells.
We have investigated the consequences of Sam68 phosphorylation on its functions and found that Sam68 phosphorylation by the enzyme Cdk1 reduces its RNA-binding ability and alternative splicing regulatory activity. During this investigation, we have incubated a region of Sam68 (its N-terminal domain) with cytoplasmic extract and to our surprise, observed that on one side, the cytoplasmic extract induces a striking structural rearrangement of this domain and on the other side, that this domain induces the formation of a macroscopic fibre composed essentially of cytoskeleton and RNA-binding proteins. This is very surprising and very exciting. This provides us with a unique in vitro system to study various fundamental processes such as the dynamics and kinetics of fibre formation, cell-extract induced protein folding and the role of Sam68 in cytoskeleton reorganization.
In this proposal we will address three complementary questions:
• What is the composition of the fibre and what are the kinetics of its formation?
• What is the structure of Sam68 N-terminal domain in cytoplasmic extracts?
• What is the role of Sam68 in cytoskeleton remodeling?
To characterize the fibre and the role of Sam68 in its formation, we will combine state-of-the-art methodologies in structural biology (nuclear magnetic resonance (NMR), mass spectrometry (MS), X-ray diffraction, electron microscopy (EM)) and cell biology (super-resolution, correlative light and electron microscopy (CLEM) and live cell imaging). Structural biology work will be undertaken in the Leicester Institute of Structural and Chemical Biology (LISCB).
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject or overseas equivalent. The University of Leicester English language requirements may apply.
How To Apply
Please refer to our How to Apply information at
With your application, please include:
• Personal statement explaining, briefly, your interest in the project and your experience ( If you apply for two projects include a statement for each project on the same document)
• Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
• Evidence of English language proficiency, if applicable
• In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available.
Dr. Cyril Dominguez
Institute of Structural and Chemical Biology
Department of Molecular and Cell Biology
University of Leicester,
Henry Wellcome Building
Leicester, LE1 7RH, UK
t: +44 (0)116 229 7073