PhD : Using yeast as to study effects of Ca2+ homeostasis on cell viability at K.U.Leuven
Project :
- Cells of all living organisms are equipped with complex signal transduction networks that enable them to regulate their growth potential and survival properties in response to changing intracellular and external signals.
- Consequently, deregulation of such signaling networks can lead to undesired cell death or cancerous growth, forming the molecular basis behind many human diseases. The yeast Saccharomyces cerevisiae is often used as a model system to unravel these complex mechanisms, as many of them appear to be highly conserved in higher eukaryotic organisms, up to the level of human cells.
- One of these conserved mechanisms in eukaryotic cells concerns calcium (Ca2+)-dependent signaling modules, which are implicated in the regulation of numerous aspects of cell growth, development and cell death in both yeast and human cells.
- An extensive network of Ca2+ channels and pumps exists that regulates Ca2+ homeostasis both in the cytosol and in multiple organelles such as the endoplasmic reticulum, vacuole and mitochondria.
- In collaboration with Prof Dr. G. Callewaert (KULAK, Kortrijk), the host laboratory is in the process of developing specific molecular probes to map Ca2+ homeostasis at these specialized cellular locations in yeast cells.
- Combined with genetic and biochemical tools, the several goals are set in this project.
- First of all, we will identify the Ca2+ channels and pumps involved in the regulation of Ca2+ homeostasis at the different organelles.
- A second goal is to study the dynamic nature of the total cellular Ca2+ homeostasis under specific physiological conditions, for instance its response to different nutrient or oxidative stresses, changes in Ca2+ homeostasis during the cellular aging process etc.
- Aside from documenting these dynamic changes in Ca2+ homeostasis, we will pinpoint the cellular players which regulate the observed changes, as well as effector molecules which respond to these changes and mediate cellular responses, such as the induction of stress defense mechanisms.
- Finally, the gained knowledge from these experiments will be applied in the study of possible involvement of Ca2+ homeostasis in the etiology of certain neurodegenerative diseases. For the latter, we will make use of humanized yeast models expressing disease-associated human genes which induce toxicity in yeast cells.
- Examples thereof include the a-synuclein and synphilin-1 genes, implicated in Parkinson's disease, or the amyloid-beta and Tau genes, associated with Alzheimer's disease.
Profile : Master in Biology, or Biochemistry or Bio-engineering
Offer : 2 year PhD contract, can be extended
Interested? For more information please contact Prof. dr. Joris Winderickx, mail: joris.winderickx@bio.kuleuven.be or Mr. Erwin Swinnen, mail: erwin.swinnen@bio.kuleuven.be.
Deadline : 15.11.14
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