Project 1:

To characterize caspase-regulated mitochondrial transport. My preliminary data suggests that mitochondrial motility promotes cell survival, which is consistent with what has been reported on the metastatic competence of tumors, and that such movement can be caspase-dependent. In Project 1, I will take a forward and reverse genetic approach to identify novel, caspase dependent, mitochondrial trafficking factors. This is an important goal as it can lead to more direct therapeutic targets to cancer. Conserved genes identified will be tested in tumor cell lines.

Project 2:

To define the role of BLMP-1/BLIMP-1 in programmed cell death. From a screen, I identified the homolog of human B lymphocyte maturation ...

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Project 1:

To characterize caspase-regulated mitochondrial transport. My preliminary data suggests that mitochondrial motility promotes cell survival, which is consistent with what has been reported on the metastatic competence of tumors, and that such movement can be caspase-dependent. In Project 1, I will take a forward and reverse genetic approach to identify novel, caspase dependent, mitochondrial trafficking factors. This is an important goal as it can lead to more direct therapeutic targets to cancer. Conserved genes identified will be tested in tumor cell lines.

Project 2:

To define the role of BLMP-1/BLIMP-1 in programmed cell death. From a screen, I identified the homolog of human B lymphocyte maturation protein, BLIMP-1, as being required for programmed cell death. BLIMP-1 is known to be associated with cancer. Project 2 involves the identification of genes downregulated or upregulated by BLMP-1/BLIMP- 1 and their role in cell death in the nematode. Following this, conserved genes will be tested first in lymphoma lines for effects on apoptosis.

Project 3:

To identify novel genes in cytoskeletal remodelling. Project 3 entails the identification of novel genes involved in cytoskeletal remodelling, a key feature of metastatic disease, from cell retraction-deficient mutants retrieved from my screens. Genes will be characterized in the nematode and those that are conserved will be tested in tumor cell lines.

Project 4:

To determine the role of kinesin-1/Kif5 in cell removal. Also from my screens, I found that the homolog of kinesin-1/Kif5, which has been proposed to be a therapeutic target against cancer, promotes phagocytosis, which has been shown to inhibit tumor progression. Project 4 aims to determine the role of Kif5 to identify what cargo it transports to facilitate phagocytosis. The role of Kif5 will also be tested in a tumor/macrophage co-culture model.

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