Aldehyde dehydrogenases (ALDHs) catalyse the oxidation and detoxification of reactive endogenous and exogenous aldehydes into carboxylic acids via NAD+ coupled reduction (Fig. 3). ALDH1 has been widely studied and is considered a marker of cancer stem cells (CSCs) and has been shown to be predictive of poor clinical outcome. Increased expression of cytosolic ALDH has been implicated as a mechanism whereby tumour cells may escape the lethality of cytotoxic anticancer alkylating agents, such as cyclophosphamide and related congeners. An improved understanding of the role ALDHs play within the tumour microenvironment and stem cell niche is crucial for unravelling their potential for biomarker and drug discovery strategies.
We are looking for an enthusiastic student who is interested in establishing opportunities for how ALDH regulation or function can be exploited for drug discovery. In particular, the high ALDH expression that is a feature of many cancer types and CSC populations might contribute to enhanced DNA repair and this project seek to investigate how such knowledge can be harnessed in drug design.
The student will be trained in 2D and 3D cell culture with a particular focus on ALDH-expressing sub-populations with stem cell properties, target interrogation (e.g. PCR, western blot, immunohistochemistry) including ALDH-chemical probe binding and effects on DNA damage response. The latter aspects will include the use of LCMS to study potential metabolic events caused as a consequence of functional ALDH activity. For students with a particular interest in chemical biology, there is also an opportunity to be trained in drug design.
Entry requirements
Applicants should have at least 2:1 honours degree in Biomedical Sciences, Chemical Biology, Pharmacy or related degree.
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