Systems biology of tumour-stroma interactions in cancer

The Cancer Research UK Cambridge Institute is a joint venture between the Charity, Cancer Research UK, and the University of Cambridge. The Institute opened in 2007 and has excellent state-of-the-art facilities. Research ranges from basic cancer biology and computational biology through to translational research and clinical application.

Graduate students play pivotal roles in the continuing success of our research programmes and gaining a studentship in the Institute is an excellent opportunity to start a research career in an environment committed to training outstanding cancer research scientists of the future.

We are excited that Dr Miller has recently chosen to join the Institute where he will continue to develop his research programme.

A Cancer Research UK-funded studentship is available for study of the following project.

Understanding how normal stromal cells communicate with cancer cells and influence tumour progression and response to therapy has the potential to dramatically alter our view of cancer biology and the way we treat cancer. New approaches to systematically characterise and model cell-cell interactions in the tumour microenvironment are needed to provide better insight into how recruited and resident stromal cells trigger oncogenesis and attenuate the efficacy of anti-cancer drugs.

We have an exciting opening for a PhD student to investigate the complex cellular interactions involved in cancer development, progression, and metastasis. The goal of the project is to identify new therapeutic targets for overcoming the problem of stroma-mediated oncogenesis and drug resistance. We will use state-of-the-art quantitative proteomics methods to systematically characterise cellular signaling processes in the microenvironment of pancreatic cancer. Using in vitro co-culture model systems of the pancreatic tumour microenvironment, we will characterise the role of fibroblasts and stellate cells in pancreatic adenocarcinoma both phenotypically and molecularly. The use of a new method for cell type-specific proteome labeling that we have recently developed will allow us to track the cell-of-origin of proteins (including secreted factors) and thereby deconvolute cell-type specific paracrine signaling events in multicellular cultures. Combining these experiments with data from the literature and from additional drug perturbation experiments, an integrative experimental-computational approach will be applied to build signaling pathway models of intercellular interactions in this disease. Such models will provide the basis for a pathway-level understanding of stroma-mediated mechanisms of drug resistance and for prediction of points of drug sensitivity that can be further tested and developed experimentally.

Preferred skills/knowledge:
We will offer training in a wide range of techniques including mass spectrometry-based proteomics, cell biological methods, cancer drug screening, as well as computational analyses of genomic, proteomic, and signaling pathway data. The ideal candidate has experience in one or more of these areas, as well as a strong interest and knowledge of cancer systems biology and/or the tumour microenvironment.

References:
Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments. Gauthier NP, Soufi B, Walkowicz WE, Pedicord VA, Mavrakis KJ, Macek B, Gin DY, Sander C, Miller ML. Nature Methods. 2013 Aug;10(8):768-73

Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets. Miller ML, Molinelli EJ, Nair JS, Sheikh T, Samy R, Jing X, He Q, Korkut A, Crago AM, Singer S, Schwartz GK, Sander C. Science Signaling. 2013 Sep 24;6(294):ra85

Perturbation biology: inferring signaling networks in cellular systems. Molinelli EJ, Korkut A, Wang W, Miller ML, Gauthier NP, Jing X, Kaushik P, He Q, Mills G, Solit DB, Pratilas CA, Weigt M, Braunstein A, Pagnani A, Zecchina R, Sander C. PLoS Comput Biol. 2013 Dec;9(12)

Successful applicants will be registered with the University of Cambridge.

Please send applications in the following format to [Email Address Removed]

• A CV, including full details of all University courses taken with date, with grades if available.
• The names and contact details of two academic referees.
• A covering letter explaining why you wish to be considered for this particular studentship, what you will bring to the project and listing your research experience to date.

The closing date for applications is 30 November 2014.