1/ generating and testing candidate transgenics in Drosophila as potential drug targets for extending healthy lifespan
2/ testing candidate drugs in Drosophila to extend healthy lifespan
3/ quantifying mtDNA deletions to understand whether and to what extent they might be fundamental causes of ageing
4/ Drug discovery: using HPLC to fractionate antibiotic, antiviral and anticancer small molecules from the surface of fly eggs.
Project 1. (Wet)
We selected Drosophila for exceptional longevity, and have RNA-seq data identifying over- or under-expressed genes in long-lived flies. These genes have homologues in humans. You will create transgenic constructs for two of these genes, using molecular biology techniques such as PCR and sequencing, cloning and ligation. They will be made as GeneSwitch-GAL4 strains. A MSc project can run a lifespan experiment testing another gene in parallel with the molecular work.
Project 2. (Wet)
We are looking for novel compounds to treat cancer in humans. We have demonstrated that Drosophila fruitflies secrete or excrete substances that have antimicrobial, antiviral and anticancer activity. This is likely to be for protection of the larvae once they emerge from the eggs. Your project will use HPLC to fractionate and purify these secretions further to try to isolate individual active small-molecule anticancer compounds. We will test fractions for effects on growth of several diverse cancer cell lines using MTS assays in 96-well plates, and examine effects on cell cycle and apoptosis using flow cytometry and fluorescence microscopy.
Project 3. (Wet)
We are looking for novel compounds to treat cancer in humans. We have demonstrated that Drosophila fruitflies secrete or excrete substances that have antimicrobial, antiviral and anticancer activity. This is likely to be for protection of the larvae once they emerge from the eggs. Your project will use HPLC to fractionate and purify these secretions further to try to isolate individual active small-molecule anticancer compounds. We will test fractions for effects on growth of several diverse cancer cell lines using MTS assays in 96-well plates, and examine effects on cell cycle and apoptosis using flow cytometry and fluorescence microscopy.
Project 4. (Mixed)
The basic molecular causes of ageing are not well understood. We are developing an assay to quantify levels of a deletion in mitochondrial DNA in single Drosophila using a real-time PCR-based technique, and a method for preparing mtDNA for deep sequencing, to characterize and quantify all the indels in a single fly. You will subject flies to a variety of treatments to see what increases and what protects against mtDNA deletions (a task impossible in humans and expensive and difficult in mice),and determine the relevance or otherwise of mtDNA deletions to ageing.
Project keywords: Ageing, Drug discovery, Antibiotics, Drosophila, mtDNA
Project types: Wet, Mixed
Find out more about Dr David Clancy here.