Structural and functional analysis of DNA repair complexes

Structural and functional analysis of DNA repair complexes

Project details

DNA damage is the most lethal threat to genome integrity and, if left unrepaired, result in cell death or in cancer. The link between DNA damage repair and cancer can be observed in the DNA repair defective disorder called Bloom’s Syndrome (Bythell-Douglas Structure 2021). Bloom’s syndrome results in cancer predisposition and hypersensitivity to chemotherapeutic agents. Due to the increased sensitivity to DNA damaging agents, targeting proteins involved in Bloom’s syndrome has been proposed as a mechanism to improve cancer treatment. This project investigates molecular mechanism of Bloom’s complex through structural and biochemical studies. 

Students will use an insect-cell expression system to produce the Bloom’s complex, followed by 1) cryo-electron microscopy and mass spectrometry to elucidate it in atomic details, and 2) biochemical reconstitution of its activity. 

 

About our research group

We are a group of structural biologists and biochemists trained in the field of virology and DNA repair. We have made major contributions in these fields by elucidating molecular mechanism of several medically relevant protein complexes (Shakeel, Rajendra Nature 2019, Alcon, Shakeel Nature Str Mol Bio 2020, Tan eLife 2020, Shakeel Nature Comm 2016 & 2017).  

The current focus of our lab is to understand the structure and function of multi-protein complexes involved in genome regulation and protection. We are a team of 1 postdoctoral scientist and 1 research assistant meaning plenty of guidance available to students. We collaborate closely with other divisions at WEHI for in vivo studies and with international collaborators in Oxford and Berlin for mass spectrometry expertise.

 

Protein structure
Structure of Fanconi Anaemia core complex, a multi-protein E3 ligase,which is required
for interstrand DNA crosslink repair (Shakeel, Rajendra et al. Nature 2019).
Photo credit: Phospho Biomedical Animation.

 

Email supervisors

 

Researchers:

Dr Shabih Shakeel

Dr Shabih Shakeel photographed at WEHI
Dr
Shabih
Shakeel
Laboratory Head

Project Type: