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Acute lymphocytic leukaemia (ALL) and diffuse large B-cell lymphoma (DLBCL) is often associated with small deletions of or point mutations in the highly related BTG1 or BTG2 genes. Even though it is known that BTG1 and BTG2 are important for proliferation and development of B- cells, it is not clear how mutations in the BTG1 and BTG2 genes contribute to tumourigenesis.
This project aims to gain further molecular understanding regarding the contribution of BTG1 and BTG2 to tumour development. These proteins interact with cytoplasmic poly(A)-binding protein 1 (PABPC1) and the multi-subunit Ccr4-Not deadenylase complex, which shortens the poly(A) tail of mRNA and initiates mRNA degradation.
The project will involve a combination of biochemical and cell-based techniques. Using recombinant proteins, the molecular details of BTG1/BTG2 interactions with PABPC1 and the Ccr4-Not subunit Caf1 will be investigated. This analysis will be complemented by cell-based techniques, including RNA immunoprecipitation (RIP) using PABPC1 antibodies and the generation of cell lines containing knockout and mutant alleles of BTG1 and/or BTG2 using Cas9/CRISPR genome editing technology.
This project provides opportunities to obtain experience with a wide range of techniques that are an excellent preparation for a variety of careers in academia or industry.
This project is open for self-funded students only. If you are a student from the EU or other parts of the world, please get in touch at an early stage to discuss possible funding opportunities.
Research output data provided by the Research Excellence Framework (REF)
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