Exploring the molecular pathways underlying orofacial cleft development

PhD project (3/4 yr research project leading to independent research at the doctorate level)

Dr Gemma Sharp, Dr Tom Gaunt, Professor Mike Dixon (University of Manchester), Aside from the expertise available at the MRC Integrative Epidemiology Unit, this project offers a unique and exciting opportunity to collaborate with world leaders in dental genetics (Mike Dixon, University of Manchester) systems biology (Professor Tom Freeman, University of Edinburgh, Roslin Institute) and biochemistry (Professor Jeremy Tavare (University of Bristol, School of Biochemistry).


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Rationale

Worldwide, every three minutes a child is born with an orofacial cleft (cleft lip/palate). These children have potential issues with feeding, appearance, speech, and hearing. Even after surgical repair, they often experience psychosocial problems throughout their lives and the condition can harm the emotional wellbeing of the whole family.

It seems most likely that clefts are caused by genetic and in utero environmental factors. With some success, many studies have attempted to identify the most important genes associated with orofacial cleft development, but much of the research on the role of these genes remains buried in the literature.

In order to interpret and focus future research efforts, there is a clear need to collate fragmented published information on genes, proteins and interactions involved in normal and abnormal orofacial development. Building and observing large integrated pathway maps can highlight important features for further investigation.

Aims & objectives

1) To systematically review literature about genes, proteins and interactions that have been previously associated with normal and abnormal orofacial development.

2) To assemble this information into a visual map of the pathways involved in orofacial development. This map would help us identify gaps in our existing knowledge and inform future studies that use the map to bridge those gaps.

3) To publish this resource online for use by the research community.

Methods

Database curation
Compile a database based on a large systematic review of the published literature around the genes, proteins and interactions associated with normal and abnormal orofacial development. Experts on hand to help with this include researchers from the University of Bristol’s School of Biochemistry and the Cleft Collective (the largest cleft research project in the world), as well as world leaders in orofacial genetics at the University of Manchester.

Pathway map construction
The pathway map would be compiled using the Modified Edinburgh Pathway Notation (mEPN) scheme, which has been pioneered by the group of collaborator Tom Freeman (University of Edinburgh).

Publication online
We will create an online resource for molecular events relevant to orofacial clefts. The website would include the full pathway map and links to key datasets and publications on orofacial cleft biology.

References

Dixon et al. Nat Rev Genet. 2011 (an introduction to cleft research)

Raza et al. BMC Syst Biol. 2010 (the use of pathway maps)

Freeman et al. BMC Syst Biol. 2010 (modified Edinburgh Pathway Notation)


Created on Oct. 1, 2015, 9 a.m.