KINFO: MSc project available

[Salli Keinänen]

MSc project available in the laboratory of Academy Professor Johanna Ivaska (http://www.ivaskalab.com/) at Turku Centre for Biotechnology

METABOLISM AS A REGULATOR OF INTEGRIN SIGNALLING AND CANCER CELL INVASION

Metastasis is the major cause of mortality in all cancer patients, but despite advances in cancer research it remains essentially incurable. Understanding the molecular and biochemical mechanisms that control metastasis is pivotal for treating cancer successfully. Cell metabolism has been increasingly recognised as a hallmark of cancer and targeting cancer metabolism has emerged as a promising strategy to inhibit tumour growth and proliferation. Although active migration of cancer cells is a prerequisite for tumour invasion and metastasis, it remains unclear whether and how metabolism regulates cancer cell migration. Metabolic enzymes make very good drug targets and several drugs are already in clinical trials. However, the effect of these drugs on tumour metastasis remains largely unknown. Integrins are cell adhesion receptors playing essential roles in health and disease and inappropriate integrin activation has been linked to cancer progression and metastasis. Hence, understanding how integrin activity is regulated is of major clinical relevance. In RNAi screens in cancer cell lines we have identified several genes involved in glucose metabolism as novel regulators of integrin activity.

The major goal of this proposal is to study whether glucose metabolism, apart from its well-described role in tumour proliferation, is important for tumour migration and invasion. Moreover, we aim to gain novel mechanistic insight into the regulation of integrin activity and signalling by cellular metabolism. The specific aims are:
1. Glycolysis and cancer cell invasion. To explore whether glucose metabolism regulates cancer cell migration and invasion using state-of-the-art imaging.
2. Glucose metabolism and integrin signalling. To study whether cell metabolism regulates integrin activity and thereby cancer cell migration and invasion.

METHODOLOGY
To address these questions, breast epithelial cancer versus normal cells will be used and the role of glucose metabolism in integrin activity, migration and invasion will be studied using siRNAs, expression constructs and metabolic drugs. The levels of integrin activity will be assessed by high-resolution microscopy and flow cytometry. Migration and invasion will be measured with state-of-the-art imaging tools. To assess cell migration the speed and directionality of the move of single cells on cell derived matrices will be measured. Invasion will be assessed in 2D and 3D culture systems and will be quantified by time-lapse microscopy.

APPLICATIONS
If you are a highly motivated and enthusiastic student, who wants to learn novel, sophisticated techniques –especially imaging–, to answer interesting and clinically relevant biological questions and to work in a dynamic, international environment please send your motivation letter, CV, academic transcripts and contact information of 2 or more references in a single merged PDF document to Acad. Prof. Johanna Ivaska, email: joivaska at utu.fi by December 31st 2015.

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Viestin välitti:

Salli Keinänen
Tiedotusvastaava, TYK ry
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