Dr Michael Taylor

Projects

Gene Function and Expression in Cell Differentiation Programs

Background: Our research centres on the genetic programs of cell differentiation that produce specialised cell-types from stem/progenitor cells.  At the heart of these programs are key transcription factors that orchestrate the expression of specific cohorts of genes.The focus of our current research is the conserved transcription factor Mef2, which is found across the breadth of the animal kingdom, and is a key player in muscle and nerve differentiation.  Much of our research uses the classic model organism, the fruit fly Drosophila melanogaster.  This system has an impressive history in making fundamental contributions to understanding human biology.

Current projects. Prospective post-doctoral fellows or PhD students interested in our work are encouraged to contact the lab.

1. Regulation of the muscle differentiation program: Our work on a gene called Him, a novel inhibitor of muscle differentiation that down-regulates Mef2 activity, has revealed a balance of positive and negative inputs controlling muscle differentiation. We are analyzing Him and other regulators to explore how progenitor cells are maintained in a committed, but undifferentiated state, and how they are triggered to enter the differentiation pathway.  We analyse both larval and adult muscle during Drosophila development. The production of adult muscles during metamorphosis is a fascinating and powerful model system for the genetic and cellular analysis of progenitor cells, tissue remodeling and regeneration.

2. Mef2 protein interactions: Central to cell differentiation programs is the organised expression of large numbers of genes in specific spatial and temporal patterns. Pivotal to this are key transcription factors like Mef2 that orchestrate the expression of specific cohorts of genes.  These factors are regulated in time and space to give different gene expression outputs.  These different outputs must result from interactions with other proteins, but it is not known how.  To answer this, our goal is a systematic analysis of proteins that interact with Mef2, both to advance understanding of the muscle differentiation program and also as an example of how the proteins in a cell interact to produce the specific transcriptional outputs that regulate cell function in health and disease.

3. Neuroscience: We are exploring Mef2 function in nerve differentiation and degeneration, and are developing models of disease for neurodegenerative conditions and movement disorders. Our approach involves using Drosophila to inform mammalian systems to best advance understanding.

4. Chromatin and differentiation programs: Genes are present in chromatin, a complex of DNA with proteins.  We are analysing how these proteins regulate how Mef2 target genes are switched “on or off” in cell differentiation programs, including muscle, nerve and heart.  The Drosophila heart is attractive as a relatively simple structure with genetic parallels to the mammalian heart.

Impact on health and quality of life: An in-depth knowledge of cell differentiation programs is critical for understanding aspects of disease and ageing, and for a range of applications, including stem cell technology and tissue repair.

Muscle disease/dysfunction - this includes the muscular dystrophies, muscle injury, and the widespread muscle weakness and degeneration associated with ageing.

Cancer - cell differentiation and cancer biology are closely linked.  Key genes in our cell differentiation studies have important roles in cancer.  Understanding how they function will inform their potential as therapeutic targets.

Stem cells - a mechanistic knowledge of cell differentiation is required to realize the potential of stem cells to produce specific cell-types for tissue repair.

Grants

• BBSRC
• EU FP6 Network of Excellence "MYORES"
• John Ryder Memorial Trust

Research group members

Ms Jun Han

Postgraduate research students

Miss Alina Cepraga

Mr Sami Chaussee

Collaborations

• Dr Eileen Furlong, Heidelberg, Germany.
• Dr Zhe Han, Ann Arbor, USA
• Dr Krzysztof Jagla, Clermont-Ferrand, France.
• Prof Eric Olson Dallas, USA.