英国癌症研究所肿瘤微环境组招聘博士后

Job Title: Post-doctoral Training Fellow – Tumour Microenvironment Team
Closing Date of vacancy: 14 February 2014
Division: Cancer Biology
Team: Tumour Microenvironment
Type of Contract: Fixed Term
Length of Contract: 36 months
Salary Range: £32,492-£40,628 p.a. inclusive (full scale)
Work Location: London
Hours per week: 35

The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes. Our mission is to make the discoveries that defeat cancer. We have a long and distinguished history of research with a major impact on the outcome for cancer patients. Our unique partnership with The Royal Marsden NHS Foundation Trust (RMH) makes us the largest comprehensive cancer centre in Europe, performing high quality original basic research and translational studies. Under the leadership of Chief Executive Professor Alan Ashworth FRS, we are committed to attracting, developing and retaining the best minds in the world. The ICR was ranked as the UK’s top academic research centre in the 2008 Higher Education Funding Council Research Assessment Exercise. Based on our publication record, citations and impact we rank among the world’s leading cancer research centres.

Main Advert Text :
Applications are sought for a Post-doctoral Training Fellow to join the recently established Tumour Microenvironment Team (led by Dr. Fernando Calvo) based in the Division of Cancer Biology at the Institute of Cancer Research, London based in Chelsea (www.icr.ac.uk).

Using a combination of intravital imaging, mouse models, mechanobiology and cell and molecular biology approaches, the Tumour Microenvironment Team focuses on understanding the role of the tumour microenvironment (TME) on tumour progression and response to therapy with the goal of developing better approaches to treat cancer.

As major components of the TME, cancer-associated fibroblasts (CAFs) will be the main topic of research. Using a multidisciplinary approach, we aim to analyse the role of the CAFs and TME in the different stages and processes of cancer progression. Intravital imaging will be used to visualise these processes and to test the mechanistic predictions of cell biology and tissue culture experiments. Importantly, a major goal of the TME team is to apply all the generated knowledge about CAF biology to translational research and clinical practice. The partnership between the Institute of Cancer Research and the Royal Marsden Hospital provides an excellent framework for it.
Specific lines of investigation to develop:
1. Characterise the mechanisms regulating CAF generation and maintenance. In particular, the importance of mechanobiological processes and the role of specific transcriptional programs and molecular players.
2. Analyse their role in different processes and stages of cancer progression. Specifically, the interplay with cancer cells and other stromal components and their co-option and function at secondary sites.
3. Study CAFs in the context of therapeutic intervention. Notably, the effect of specific therapies on fibroblast phenotype, the role of CAFs in resistance to therapy and residual disease, and the design of alternative routes to target CAFs as a therapeutic approach.

Occasionally, the group will also test specific molecular players in a cancer cell setting – we are particularly interested in mechanisms acquired by cancer cells during metastatic spread or therapeutic resistance that are usually exclusive of stromal cells. We believe that the knowledge generated on characterising such mechanisms on CAFs will provide an ideal platform to address this type of studies.

The group has already optimised a set of tools and systems to address these lines of investigation. One of our goals is to expand these tools and develop novel approaches that will broaden our research to eventually fully address our goals. In particular, we aim to improve intravital techniques to visualise multiple cellular types and thereby study heterogenous interactions in vivo, as well as to develop approaches to visualise the metastatic process at secondary sites. We also aim to establish mouse models to specifically knock-down or knock-in genes on CAFs. Finally, tumour models to examine TME implication in therapy are also in the scope.

This is an excellent opportunity a motivated, determined, independent and creative scientist to work in an exciting and highly collaborative environment. By becoming part of a young and enthusiastic team, the successful candidate will contribute through multi-disciplinary efforts to the understanding of TME. The Institute of Cancer Research also provide a wide variety of training opportunities.

Essential requirements for this post include a PhD or equivalent in a relevant subject with the appropriate experience and track record. A good knowledge of tissue culture, molecular and cellular biology approaches, biological assays and cancer biology in general is essential. A demonstrated ability to communicate well, work within a team and maintain good laboratory records are also expected. Experience on 3D culture systems, mechanobiology, microscopy, live imaging, mouse genetics and handling, primary cell culture and cancer models will be advantageous. The recipient will be expected to coordinate with other members of the team and the Division and to have a strong ability to contribute to a multidisciplinary collaboration through providing scientific input into a developing research project.
The appointment is offered on a fixed-term contract for 36 months in the first instance, with a starting salary in the range of £32,492-£34,944 p.a. inclusive (based on previous post-doctoral experience). The position is immediately available but will be open until a suitable candidate is found. Ideally, the post will begin before Summer 2014. While this project is currently funded by the Institute of Cancer Research, an integral part of the postdoctoral training is the process to preparing a research proposal and writing a fellowship application. The Postodoctoral Fellow will be encouraged to apply for external funding.

Suggested readings:
- Calvo, F., Ege. N., Grande-Garcia, A., Hooper, S., Jenkins, R.P., Chaudhry, S.I., Harrington, K., Williamson, P., Moeendarbary, E., Charras, G. and Sahai, E. (2013). Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol. 15(6):637-46
- Calvo, F., Sanz-Moreno, V., Agudo-Ibáñez, L., Wallberg, F., Sahai, E., Marshall, C.J. and Crespo, P. (2011). RasGRF suppresses Cdc42-mediated tumour cell movement, cytoskeletal dynamics and transformation. Nat Cell Biol. 13(7):819-26.
- Calvo, F. and Sahai, E. (2011). Cell communication networks in cancer invasion. Curr Opin Cell Biol. 23(5):621-9.
- Hanahan, D. and Coussens, L.M. (2012). Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21(3):309-22.
- Kalluri, R. and Zeisberg, M. (2006). Fibroblasts in cancer. Nat Rev Cancer. 6(5):392-401.