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Förslaget inkom 2008-05-30

Kindlins - a novel family of integrin-interacting proteins: crystal structure, biological function and role in human cancers

OBS! ANSÖKNINGSTIDEN FÖR DETTA EXJOBB HAR LÖPT UT.
We and others have suggested that kindlins, a family of newly discovered integrin-interacting proteins, play important roles in inetgrin-mediated biological functions as well as in human diseases including cancers. It is known that more than 90% of cancer patients’ death was caused by the invasive growth and metastases of tumor cells. The metastases of cancer cells were mediated by integrins, the major transmembrane receptors for the extracellular matrices (ECM). Integrins contact the ECM via their N-terminal extracellular domains and connect to the intracellular environment via their C-terminal cytoplasmic domains, and thereby mediate cell adhesion, cell motility and transmit signals from the ECM into the cell, regulating cell differentiation, proliferation and survival. We have identified that kindlins bind to the integrin C-terminal cytoplasmic domain in a yeast two-hybrid screening and in biochemical assays. Knock-down of endogenous kindlins impair inegrin-mediated cell spreading, adhesion, migration and invasion as well as cell proliferation. These are important biological functions that kindlins involved and correlate to the potentiality of cancer cell metastases. We found that kindlins are overexpressed in human cancers including malignant mesothelioma, prostate cancer, colon cancer and lung cancer. Therefore, we plan to elucidate how kindlins are involved in these processes and what consequences that kindlins lead to in the disease situations.
For 20 points students, I have projects for the following topics:
1. Protein-protein interactions in the integrin-mediated cellular signaling. The related techniques are the yeast two-hybrid screening, co-immunoprecipitation, pull-down assay, Biocore and cell staining. The students have chance to lear and practice the most usful knowledge for finfding new signaling molecules.
2. Protein expression in mammalian cells and in E.coli for the purposes of functional analysis and protein crystal structure establishment. The students will learn and practice with the knowledge of protein expression, purification, protein crystal growth, and much more on the protein chemistry.
Group composition: We are the Department of Biosciences and Nutrition at Novum and the Unit for Clinical Molecular Biology,and the Unit Dirctor is Docent Staffan Strömblad. I, Hongquan Zhang, Ph.D., am a senior Forskare and principal investigator and my research is supported by Cancerfonden and VR in Sweden. We have a very good working environment both socially and academically.

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