Research Fellow in Structural and Computational Biology Many of the proteins that are critical for cancer development are intrinsically disordered or have large disordered regions. Moreover, the genetic alterations that promote cancer generate mutated forms of proteins that are destabilized. One example is the fusion protein formed from the microtubule binding protein EML4 and the tyrosine kinase ALK. The EML4-ALK fusion is the key driver in approximately 5% of non-small cell lung cancer (NSCLC) patients. Alternative breakpoints in the EML4 gene result in fusion proteins of different lengths and properties, and patients with longer forms respond better to treatment that those with shorter forms. We do not understand why this is the case, but we hypothesize that it is due to differences in protein stability and protein-protein interactions. The longer forms of EML4-ALK, found in two-thirds of patients, include only part of a tandem beta propeller (TAPE) domain. The broken TAPE domain does not impede the expression of the fusion protein, or inhibit the catalytic activity of the fused ALK kinase, and contributes directly to cancer signaling. This is remarkable because the folding of the broken TAPE domain should be severely compromised.
We are looking for a Research Fellow to explore the structural dynamics and interactions of disordered regions of proteins of relevance to cancer, starting with the broken TAPE domain of EML4-ALK. You will explore the structure and dynamics of the broken TAPE domain in the fusion protein, characterize its molecular interactions and decipher the molecular mechanisms that underpin cancer signaling. Approaches will include molecular simulation, biophysical characterization of protein folding and advanced mass spectrometry. We have a long-standing interest in intrinsically disordered proteins and their interactions, protein kinases and cancer signalling. The post is funded by a Programme Award from Cancer Research UK, which supports a thriving research group embedded in the Astbury Centre<http://www.astbury.leeds.ac.uk/> for Structural and Molecular Biology. To explore the post further or for any queries you may have, please contact: Richard Bayliss<http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=RWB>, Professor of Molecular Medicine Tel: +44 (0)113 343 9919, email: <mailto:[email protected]> [email protected]<mailto:[email protected]> Location: Leeds - Main Campus Faculty/Service: Faculty of Biological Sciences School/Institute: School of Molecular & Cellular Biology Category: Research Grade: Grade 7 Salary: £32,548 to £38,833 p.a. Due to funding limitations an appointment cannot be made above £34,520 p.a. Working Time: 100% Post Type: Full Time Contract Type: Fixed Term (until 28 February 2020, potential to extend for further 24 months - due to funding) Closing Date: Tuesday 02 January 2018
