Targeting the EML4-NEK9-NEK7 complex in drug-resistant EML4-ALK lung cancer

Leicester Institute of Structural and Chemical Biology (LISCB)

PhD Start date: September 2020

Lung cancer is the largest cause of cancer-related deaths. While little progress has been made in long-term survival rates, we now have a good understanding of the genetic drivers. 5% of lung cancers are driven by the EML4-ALK oncogenic fusion and these initially respond well to targeted ALK inhibition. However, patients inevitably relapse and there is a need for new therapeutic approaches. We have discovered an ALK-independent pathway that drives metastatic dissemination of these cancers. This involves formation of a complex between EML4 and the NEK9 and NEK7 kinases. In this PhD project, we will first use a structural biology approach to map interacting domains and define the molecular nature of the EML4-NEK9-NEK7 complex. Second, we will use molecular cell biology techniques to test for the presence of this complex in tumour samples and whether ALK inhibitors or approaches that inactivate NEK9 and NEK7 prevent downstream changes that drive metastasis.

Academic entry requirements:
UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.

How to apply: https://le.ac.uk/study/research-degrees/funded-opportunities/cls-mcb-liscb-2020

Eligibility:
UK and EU candidates only