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Structural biology of signal transduction

A postgraduate research opportunity at the University of Otago.

Details

Academic background
Sciences, Health Sciences
Host campus
Dunedin
Qualification
PhD
Department
Biochemistry
Supervisor
Associate Professor Peter Mace

Overview

Our group has a range of potential PhD projects available related to understanding the mechanisms that underly efficient signal transduction, and gene expression. Because we work at the molecular level, understanding these signaling pathways is relevant to both human disease, and in plant stress responses.

Several projects are available investigating proteins involved in post-translational modifications such as phosphorylation and ubiquitination. We use a combination of molecular biology, X-ray crystallography, electron microscopy and biochemical assays. Please contact Peter Mace to discuss relevant projects that may be best suited to your background and interests.

Applications will be assessed on a rolling basis.

How do stress signals activate kinase signaling?

Stress-activated protein kinases control cellular responses to either chemical or inflammatory danger, and can either enhance or impede treatment of cancer and inflammatory disease. However, our knowledge of how they recognise and respond to stress signals is surprisingly limited. We are particularly interested in two types of human stress-activated protein kinase: the apoptosis signal-regulated kinases (ASK1–3), and MEKK1. We have solved crystal structures of domains from each of these kinases. Potential PhD projects will use biochemistry and structural biology of larger proteins to understand regulation of how they are regulated by forming larger signaling hubs, and binding to additional structures within cells.

ASK_SAXs

At the protein level plants and humans have similar stress-activated kinase networks, which plants use extensively to sense and respond to stresses such as drought and heat. We have a growing interest in how stress-activated kinases are regulated in plants and several target kinases for structural investigation, suited to potential students with an interest in plant biology.

Regulation of transcription factors by ubiquitin modifications

Ubiquitin modifications can elicit protein degradation or other signalling functions. We have two ubiquitin-related projects that both relate to activity of a ubiquitin ligase called COP1, and aim to explore:

  • how ‘Tribbles’ pseudokinases work with called COP1 to transfer ubiquitin onto transcription factors that control myeloid differentiation, and leukaemia. This project will also employ protein nanobodies to advance Tribbles as drug targets.
  • How the COP1 protein in plants is regulated in response to UV light. Like its human ortholog, plant COP1 mediates ubiquitination of transcription factors. Plant COP1 is a central regulator of photomorphogenesis (the response to UV light), which impacts various aspects of plant physiology, but little is structurally understood about its regulation.

Due to the ongoing COVID-19 pandemic, some restrictions may be in place. Visit otago.ac.nz/coronavirus for ongoing updates:
- International students


New Zealands borders are closed due to the Covid-19 pandemic processing applications from overseas will be delayed

Contact

Associate Professor Peter Mace
Email   biochem.phd@otago.ac.nz