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Investigating the process of cancerization in lung squamous cell carcinoma by sequential genetic engineering of primary human basal cells


About This PhD Project

Project Description

4 Year CRUK PhD Studentship – September 2019

Despite novel therapeutic modalities, non-small cell lung cancer (NSCLC) is still an unmet need in lung cancer research, particularly in the area of early diagnosis and the treatment of the advanced disease, where existing therapies have little effect (less than 20% of stage 4 patients survive more than 1 year after diagnosis). Lung squamous cell carcinoma (LUSC) is a frequent subtype of NSCLC (40%). It is strongly associated with cigarette smoking and presents specific cellular and genomic traits fully differentiated from the rest of lung cancer types. LUSC arises from the accumulation of genetic changes of basal cells, the resident stem cells in the proximal bronchial epithelium, affecting key cellular processes such as the squamous differentiation pathway among others.

The Clinical and Experimental Pharmacology Group, led by Professor Caroline Dive [CBE], has a long-standing trajectory in translational lung cancer research, pioneering the use of liquid biopsies to develop novel clinical biomarkers (Carter et al., 2017, Morrow et al., 2016). The aim of this project is to investigate the process of cancerization in LUSC by sequential genetic-engineering of human basal cells. With this strategy, we intend to identify the crucial genomic events that determine the transformation of basal cells as well as develop a human model of LUSC that will compliment and improve the existing preclinical models. The student will work in close collaboration with Dr Carlos Lopez-Garcia in this project and will perform a wide range of cell biology and molecular techniques, including Crispr/Cas9, 3D-organotypic cultures and next-generation sequencing. This project also offers an ideal educational opportunity, acquiring a wide range of experience and multidisciplinary knowledge on cancer biology and genetics in a world-class scientific environment.

Studentships are fully funded for 4 years commencing September 2019. Cancer Research UK sponsorship includes generous stipend, tuition and bench fees. Students trained within our research groups will matriculate from the University of Manchester. This project will be based at the CRUK Manchester Institute Alderley Park site, Cheshire.

Applications are invited from exceptionally high calibre students, graduates or final year undergraduates who should hold or are expected to gain a first/upper second-class honours degree in a relevant subject as part of a University degree course.

Informal enquiries should be addressed to Dr Carlos Lopez-Garcia;

Interested students can find full project details, entry criteria and details on how to apply on the CRUK Manchester Institute website;
http://www.cruk.manchester.ac.uk/education/PhD-Studentships

Closing date: Monday 18 March 2019, 1700 hrs (GMT)

Interview date: Thursday 11 April 2019, Alderley Park, Cheshire

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