Investigating the cross-talk between the cytoskeleton and the nucleus in cancer

Metastasis is the cause of death of 90% cancer patients. The Sanz-Moreno lab is interested in the cytoskeleton of cancer cells and how such cytoskeleton may regulate the ability of metastatic aggressive migratory cells that can survive in a foreign environment. We have shown that the actomyosin cytoskeleton is able to coordinate this difference in metastatic behavior using a very fine-tuned crosstalk with several transcription factors in the nucleus. We have shown that perturbations of the cytoskeleton can affect transcription factor activity Specifically, Rho-Kinase (ROCK) is a major regulator of cytoskeletal dynamics, and we found that inhibition of its kinase activity results in dramatic changes in transcriptional responses associated with metastatic potential. We have shown that some transcription factors are activated or suppressed by ROCK (1,2,3,4) but we still don’t know precisely how.

In this project, the student will gain further understanding on the nature of such a regulation, is it via direct phosphorylation? Is it via formation of macromolecular complexes? is it via indirect regulation of signaling intermediates? Furthermore the student will try to identify novel strategies of targeting such a regulation to stop metastatic dissemination. This exciting project is multidisciplinary in nature and combines cell and molecular biology, biochemistry and translational medicine. The student will acquire a range of molecular biology skills including biochemical assays: co-immunoprecipitation, isothermal titration calorimetry (ITC), SEC-MALLS and kinase assays. It will be combined with cell biology and state of the art microscopy, including time-lapse video-microscopy and confocal imaging to study cytoskeletal organization and cell migration. We will also analyze transcriptional responses using traceable gene reporter assays and transcriptomic approaches. Furthermore it will make use of in vivo mouse models of cancer to understand if the crosstalk between the cytoskeleton and transcription factors could be targeted in the clinic for patients with aggressive metastatic cancers.

1. Sanz-Moreno, Cancer Cell, 2011 2. Orgaz, Nat Comm, 2014 2. Cantelli, Curr Biol, 2015 3. Herraiz, JNCI, 2015

Training: All students are regularly notified about skills development opportunities through a monthly Postgraduate Research Newsletter. Participation in the annual Postgraduate Research Symposium is compulsory for all students and provides an opportunity to improve science communication and presentation skills. All postgraduate students in the Randall present their research in seminars to the whole division as well as to their research groups. Opportunities are available for postgraduate students to present their work at national and international scientific meetings. Our postgraduate students also assist with teaching of undergraduates as demonstrators in practical classes or leading tutorials.

Academic requirements: Minimum Upper Second (above 60%) BSc or an MSc degree in Biology or Biochemistry.

English Language requirements: Applicants are required to meet the English Language requirements for Band D as set out in https://www.kcl.ac.uk/study/postgraduate/apply/entry-requirements/english-language.aspx

Start date: 01/10/2017

How to apply Please apply online at https://apply.kcl.ac.uk/ following these steps: 1. Register a new account /login. 2. Open a new application 3. Under Choose a programme: a. Select - Research programme b. Keywords- enter Randall and then search c. Select ‘Randall Division of Cell and Molecular Biophysics MPhil/PhD (Full-time)’ d. Select September 2017 as the start date (for 1 October 2017 start). 4. Complete your application PLEASE NOTE: Applicants must include the project reference number 17/RDCMB/S03 in the ‘Research proposal’ and ‘Funding (point 5)’ sections of the applications, and specify Dr Victoria Sanz-Moreno as the supervisor. Interviews are planned to be held mid-August.

It is highly recommended to informally approach Dr Victoria Sanz-Moreno ([Email Address Removed]) in advance of applying.
For administrative and application process enquiries please contact [Email Address Removed].