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Biochemistry and Biomedical Science Projects
Faculty Name.
Room No: .............Emai:
Project Title Cell Biology of Fission Yeast
Project Type:
Exp
Project Title: Cell Biology of Fission Yeast
Possible Titles
1. Invasive growth in Fission Yeast
Further Information
Fission yeast is usually considered a model single-celled eukaryote. However, we found that it can differentiate into elaborate multicellular structures which invade the growth medium. This switch in form is critical for infection for pathogenic yeasts which are much harder to study. We have identified groups of genes required for the process. The project will involve studying these by in vivo microscopy, proteomics or genetics to understand the role of each. One long-term aim is to extrapolate the results to pathogenic yeasts and identify new approaches to treating infection.
2. Functional genomics of fission yeast vacuoles
Vacuoles are the yeast equivalent of lysosomes, which are implicated in a range of diseases and required for autophagy. We have a new collection of fission yeast mutants each deleted in one gene from the genome, and are using it to identify genes required for several different processes of vacuole trafficking and biology. The project may involve identifying these genes by microscopy, analysis by genetics, and bioinformatics to understand the ’phylogeny’ of these genes: which are found only in yeasts, and which in all eukaryotes, including humans?

Project Area: Molecular genetic analysis of populations
Further Information
The projects will involve the use of molecular markers to investigate polymorphisms in DNA extracts from multiple individuals. We mostly work on amphibians (frogs, toads) and insects (beetles). The main techniques involved (DNA extraction, PCR amplification, electrophoresis, data analysis) are however of wide relevance, including to forensic study based on DNA fingerprinting.

وهذي للدراسات العليا

.
Molecular & cell biology
Role of the Fibroblast Growth Factor Receptor in regulation of membrane traffic.

Background:
Membrane trafficking pathways target various molecules to their specific destinations within the cell as well as in and out of the cell, and thus are essential for fundamental aspects of eukaryotic life. Importance of these pathways is illustrated by the growing number of diseases and cancers associated with defects in these pathways 1,2. Mounting evidence indicates that membrane trafficking and signalling are intimately linked and use common molecular components. The hypothesis of signalling and membrane traffic regulation from the intracellular membrane compartments is further supported by numerous reports showing the presence of various signalling molecules on endomembranes 3. Intracellular membranes are important sites for receptor-mediated signal transduction; they contain activated receptors and their downstream effectors thus playing a role in active signal transduction via compartment-specific interactions. Recently, we performed a genome-wide screen in C.elegans to identify novel membrane trafficking regulators. The worm Fibroblast Growth Factor Receptor (FGFR) together with several downstream effectors were found as candidate regulators of membrane trafficking in the screen, thus making the FGFR and FGFR-mediated signalling pathway an excellent candidate to exploit in order to understand how membrane transport regulation is accomplished through signal transduction 4. The FGFR signalling pathway has been relatively well defined in C.elegans by using genetic screens, which have identified FGFR downstream effectors many of which are conserved in mammalian FGFR signalling (reviewed in 5). FGFR signalling in C.elegans is initiated by 2 different FGFs, and downstream signalling is transmitted either through activation of MAP kinase pathway or through activation of phosphatidyinositol 3-kinase/AKT kinase pathway. The broad aim of this study is to determine how regulation of membrane trafficking is achieved through signal transduction.
Project:
Powerful genetics of C.elegans has been proven to be beneficial in studying membrane transport and cell signalling pathways in vivo, and therefore will be used in this project. To determine which step of membrane trafficking is impaired by FGFR signalling cascade we will analyse changes in intracellular membrane compartments by knocking down or overactivating the function of individual components of the FGFR signalling cascade. Observation of a change in the subcellular localization or morphology of any membrane compartments would indicate a role for a protein in a particular step in membrane trafficking.
We will also analyze the subcellular localization of FGFR signalling cascade components. Localization of FGFR signalling components on intracellular membrane compartments could suggest FGFR signalling from these compartments and/or signalling-mediated control of membrane traffic. Another aim of the project is to determine the downstream targets of FGFR signalling involved in regulation of membrane trafficking. Once we have a clue on the role of FGFR signalling role in membrane trafficking in C.elegans we will determine if similar regulatory mechanism are conserved in mammalian systems.

References.
1 Aridor, M. and Hannan, L.A. (2000) Traffic 1, 836-51
2 Olkkonen, V.M. and Ikonen, E. (2006) J Cell Sci 119, 5031-45
3 Sallese, M., Pulvirenti, T. and Luini, A. (2006) Embo J 25, 2663-73
4 Balklava, Z., Pant, S., Fares, H. and Grant, B.D. (2007) Nat Cell Biol 9, 1066-73
5 Birnbaum, D., Popovici, C. and Roubin, R. (2005) Dev Dyn 232, 247-55[/QUOTE]