Regulatory Proteins in Development and Disease

Summary

PhD projects in this laboratory are focused on understanding how key proteins can lead to both normal development and disease, and using this knowledge to develop reagents to inhibit or enhance specific cellular processes.

Supervisor(s)

Dr Jacqui Matthews

Research Location

School of Molecular Bioscience

Program Type

Masters/PHD

Synopsis

The 30,000 or so genes in your genome encode proteins that work together in a coordinated fashion to regulate every biological process in your body. We want to find out, not just how proteins achieve these important biological processes, but also whether we can artificially regulate these activities through the design of specific protein inhibitors. In particular, we are investigating the protein:protein and protein:DNA interactions that occur during normal cellular development (such as blood cell and neuronal development) and comparing them with interactions that cause leukemia and breast cancer. Our focus is on the regulatory complexes made by a family of LIM containing proteins, the LMO (LIM-only) transcriptional regulators and the LIM-HD (LIM-homeodomain) transcription factors. LMO2 is essential for the development of blood cells, and its abnormal overproduction is a direct cause of T cell acute lymphoblastic leukemia (T-ALL). LMO4 is involved in the development of the breast epithilium and is a breast cancer oncogene, being overproduced in half of all breast cancers. LIM-HDs are expressed in different permutations and combinations to regulate neural development and distinct cell types in the brain. We are defining the key biomolecular interactions made by these proteins and are developing inhibitors of these interactions that can be used as research tools to uncover biological function, and could ultimately be used to treat disease.

Additional Information

To do this, we use a wide range of different techniques including molecular biology (cloning/mutagenesis/ engineering), protein production and purification, and a wide range of biophysical (Yeast two-hybrid, phage display, ITC, EMSA, etc.), and structural methods. This is a fairly wide area of research and PhD projects can be designed to suit the student in many different specific areas.

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Keywords

Leukemia, Breast Cancer, blood cell development, neural development, Biomolecular interactions, protein chemistry, Structural biology, molecular biology, Biophysics, drug design, protein engineering, Cancer & leukaemia, Cell biology, Genes in biology & medicine, Human body, Neuroscience & psychology

Opportunity ID

The opportunity ID for this research opportunity is: 43