Structural investigation of oncogenic splicing factors

More than 90% of human genes can and do express multiple proteins. This is achieved by a process called alternative RNA splicing, which is an essential step in gene expression in mammals. In human, more than 100,000 proteins are produced from only 20,000 genes. For example, neurexin 3 alone is believed to express 1,728 different proteins with different synaptic functions from one pre-mRNA sequence.

Alternative splicing dictates which protein to express; this varies between tissues, development stages or in response to extracellular environment and the choices made affect processes ranging from memory and differentiation to death and disease.

Alternative splicing is regulated by many RNA-binding proteins, called splicing factors, in the nucleus. Through binding to the pre-mRNA, these proteins will compete or cooperate to induce the inclusion or exclusion of certain exons. However, the molecular mechanisms governing these regulatory events are still largely unknown. Mutations of overexpression of these splicing factors are associated with cancer progression.

Our laboratory is interested in the molecular basis of splicing regulation by studying the specificity of protein-RNA interactions and the role of post-translational modifications on splicing factor functions. To that aim we use a multidisciplinary approach combining biochemistry (protein expression and purification, in vitro translation and purification of RNAs, ..), structural biology (NMR, X-ray crystallography, and cryo-EM), biophysics (single-molecule microscopy, ITC, SPR, …), and cell biology (fluorescence and confocal imaging, cell-based splicing assays, …).

The project will focus on deciphering the function and regulation of the splicing factor Sam68 that display oncogenic properties and is overexpressed in numerous cancers. 

Entry requirements

• Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.
• Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.
• Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.
• Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.
• Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above.
• University English language requirements apply.

To apply

Carefully read the application advice on our website below and submit your PhD application. 

https://le.ac.uk/study/research-degrees/research-subjects/molecular-and-cell-biology