Involvement of the matrix protein SPARC in the dynamic interaction between tumour and host cells
Tumour growth depends on the crosstalk between malignant and surrounding stromal cells (fibroblasts, osteoblasts, endothelial cells and inflammatory cells). Malignant cells secrete soluble proteins that reach neighbouring stromal cells, forcing them to provide a suitable 3D environment for their growth and spreading (metastasis). Different studies, including expression array analysis, identified the matrix protein SPARC as a marker of poor prognosis in different types of cancer.
Growth factors, like TGFbeta and PTHrP, play a role in tumour progression by modulating protein expression. However, little is known of how these external factors modulate the intracellular trafficking machinery to stimulate secretion of proteins such as SPARC.
The main aim of the project is to elucidate how aberrant growth factor signalling alters protein secretion. To investigate the effects of TGFbeta and PTHrP on SPARC secretion, we plan to use tumour cells and primary osteoblastic cells known to naturally express SPARC. We will study secretion of endogenous SPARC by immunoprecipitation as well as by measuring secretion of Green Fluorescent Protein-SPARC chimerae in response to treatment with TGFbeta and PTHrP. TGFbeta and PTHrP signalling most likely stimulates GTP exchange factors (GEF) that are specific for the small GTPases of the ARF and Rab family. We will therefore study SPARC secretion before and after knockdown of selected GTP-exchange proteins with small interfering RNA.
How to apply
If you are interested in applying for the above PhD topic please follow the steps below:
- Contact the supervisor by email or phone to discuss your interest and find out if you woold be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
- Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
- Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.
This is a self funded topic
Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.
Meet the Supervisor(s)
- Qualifications: -
- 1993: PhD in Chemical Technology/Biochemistry, Technical University Darmstadt, Germany
- 1989: German equivalent of BS/MS degree in Chemical Technology, Technical University Darmstadt, Germany
- Dr Manos Karteris graduated with a BSc (Hons) in Medical Biochemistry from the University of Surrey in 1995. He then was awarded an MSc with Distinction in Medical Genetics with Immunology from Brunel University London in 1996 and completed his PhD in Molecular Endocrinology from the University of Warwick in 2000. He then undertook post-doctoral appointments at the University of Warwick, including a prestigious VIP Research Fellowship from the Wellcome Trust. He was appointed as Lecturer in Endocrinology at the University of Warwick from 2005-2006 and then he transferred to Brunel University London as a Lecturer in Biomedical Sciences in June 2006. In October 2017 Dr Karteris became a Senior Lecturer in the Division of Biomedical Sciences. He is also the head of the Cancer Biomarkers and Cellular Endocrinology Lab (CBCEL). For more information please visit the lab webpage: www.cbcel.org
BSc Medical Biochemistry, University of Surrey
MSc Medical Genetics with Immunology, Brunel University
PhD Molecular Endocrinology, University of Warwick
PGCert HE & PGCERT IP Law, Brunel University
Related Research Group(s)
Organ-on-a-Chip - The group’s main research focus is on women’s health and developing four main organ-on-a-chip (OOC) models: the breast, vagina, ovary, and placenta.