Chemical Biology in Drug Discovery Laboratory - Honours projects available in 2010
An Honours project undertaken in this lab would be administered by the Discipline of Pharmacology.
Our group uses a chemical biology approach to access and characterise molecules (proteins, secondary metabolites) that provide platforms for drug design and drug discovery (antibiotics, anticancer agents, iron-overload treatments). Our principal interest lies in a class of molecules called siderophores (Greek for 'iron carrier'), which are produced by pathogenic and non-pathogenic bacteria in order to sequester iron, which is an element fundamental for life. Hydroxamic acid-based siderophores have therapeutic applications for patients with beta-thalassemia who suffer from iron-overload disease. The metal-binding capacity of siderophores and siderophore mimics has exciting applications in the treatment of cancer and for the design of new antibiotics that exploit the regular bacterial iron-uptake pathway. We are also isolating siderophores from bacteria that reside under environmental extremes ('extremophiles').
- Novel histone deacetylase inhibitors
Supervisor + contact details:
- Dr Rachel Codd
Histone deacetylases (HDACs) play a role, together with histone acetyltransferases, in the regulation of the level of acetylation of lysine residues of nucleosomal histones in chromatin, which is an important determinant of transcriptional activity. Inhibition of HDACs yields hyperacetylated histones, which results in a more relaxed chromatin structure that is more readily accessed by the transcriptional machinery, thereby increasing transcriptional activity. Hydroxamic acid-based compounds have been found to inhibit HDACs and to induce cell differentiation in selected leukemia cell lines - as a result, compounds of this class are at the forefront of oncology research.
- Capture of bacterial secondary metabolites
Supervisor + contact details:
- Dr Rachel Codd
A new technique has recently been developed in our laboratory which has implications for capturing secondary metabolites (siderophores, antibiotics) produced by microorganisms. This technique is set to define a new era in biodiscovery and has significant implications for streamlining pharmaceutics processing. In this project, you will optimize the technique for the capture of a series of antibiotics and will examine the efficacy of the technique for capturing these antibiotics from bacterial culture supernatants of Streptomyces species.
- Mechanisms of iron uptake in antarctic bacteria
Supervisor + contact details:
- Dr Rachel Codd
Antarctica is considered an iron desert, due to the very low Aeolian (wind-borne) iron influx that reaches this geographically isolated continent. Coupled with the cold waters of Antarctic, which will affect the solubility of iron (oxy)hydroxides, marine bacteria indigenous to the Antarctic will have evolved novel iron uptake mechanisms to meet their fundamental iron requirement. In this project, you will culture three Antarctic bacteria under iron-deprived conditions and isolate and characterize the native 'cold-adapted' siderophores. These 'super-siderophores' may find new therapeutic applications.
- Selective capture of bleomycis streptomyces verticillus
Supervisor + contact details:
- Dr Rachel Codd
Bleomycins are a family of metal-dependant glycopeptide-based DNA-cleaving antibiotics produced by Streptomyces verticillus, which are used in combination therapy for the treatment of Hodgkin’s disease, head and neck cancer, certain lymphomas and testicular cancer. The complexity of the structures of bleomycins and the related phelomycins prevents laboratory preparation; access to these compounds, therefore, relies on fermentation. Our laboratory is using an affinity-based capture technique for expediting access to biomedically relevant bacterial secondary metabolites. In this project, you will examine the potential of the technique to capture molecules that model the metal-binding region of bleomycins as a prelude to capturing bleomycins direct from bacterial culture. During the course of the project, new molecules, aside from bleomycins, may be discovered. A successful outcome to this project will provide a rapid and high yielding route to bleomycins using green technology that will have significant advantages above current processing approaches. This project will suit a student with an interest in chemical biology, molecular biotechnology and/or microbiology.
