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Thesis topic proposal
 
The role of plasma membrane Ca2+ ATPases in cancer cell migration

THESIS TOPIC PROPOSAL

Institute: Eötvös Loránd University, Budapest
biology
Doctoral School of Biology

Thesis supervisor: Ágnes Enyedi
Location of studies (in Hungarian): Molecular Oncology Research Group of the Hungarian Academy of Sciences and Semmelweis University, 2nd Institute of Pathology, Budapest, Hungary
Abbreviation of location of studies: MTA


Description of the research topic:

Our group focuses on studying the plasma membrane Ca2+ATPases (PMCAs). The basic function of these transport proteins is to restore the resting low intracellular calcium level by the extrusion of excess calcium from the cytosol after different kinds of cell stimuli. Thus, these calcium transport ATPases play a crucial role in the regulation of cellular calcium homeostasis. Numerous observations indicate that remodeling of cellular Ca2+ homeostasis is an important step of tumorigenesis and metastasis formation. An altered expression of the PMCA has been reported in a variety of cancer cell types that was accompanied by a significantly altered Ca2+ signaling pattern hence, our aim is to study the role of PMCA in these processes. We induce differentiation or apoptosis, or manipulate cellular proliferation in normal and tumor cell lines in vitro and examine the changes in the expression, cellular distribution, changes in structure/function and intermolecular interactions of the PMCA with other proteins. We apply various fluorescent calcium indicators to monitor the effects of the altered PMCA patterns on cellular calcium levels. Since migration of tumor cells often leads to tumor-cell invasion and metastasis - which is the major cancerous process that causes death - our most recent studies focus on the role of Ca2+ signaling in melanoma and breast cancer cell migration. We intend to study the spatial organization of calcium signaling elements such as the PMCA in migrating cancer cells. We will determine specific localization/sorting motifs of the PMCA and study how these motifs affect its localization pattern. We will study the spatial distribution of Ca2+ signaling by using targeted sensors and detect local calcium signals near distinct cellular compartments: near the plasma membrane or the actin cytoskeleton. Proper control of Ca2+ signaling is critical for cell physiology and health, and disturbances in cellular calcium homeostasis can result in the development of cancer. Therefore, these studies could contribute to the understanding of the biochemical and cellular mechanisms underlying the development of serious diseases such as melanoma or breast tumors and the risk of metastases.

Required language skills: English
Further requirements: 
Experience with essential laboratory techniques, mammalian cell culture, statistics, excel and other other Microsoft Office applications.

Number of students who can be accepted: 1

Deadline for application: 2016-05-31


2024. IV. 17.
ODT ülés
Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).

 
All rights reserved © 2007, Hungarian Doctoral Council. Doctoral Council registration number at commissioner for data protection: 02003/0001. Program version: 2.2358 ( 2017. X. 31. )