Research groups

Research

Molecular biology of mammalian fertility:

• Evolution of the MDC family of proteins in C. elegans and man

  MDC proteins are expressed in a wide range of eukaryotic species (from C. elegans to man) where they have been implicated in diverse functions ranging from cell signalling to sperm-egg binding. Most MDC work has focussed on mammals. However, because of the large number and sequence similarity, identifying species orthologues is difficult, particularly when the function of many of them is unknown. What is needed is a simpler model organism in which there is a more limited number of MDC genes, and where knockouts to obtain an indication of function has been, or is easily, obtained. We have therefore interrogated the C. elegans genome and identified 10 MDC homologues. This project will use a combination of computational and experimental bioinformatics approaches to study the evolution and inter-relationship of these worm homologues in the context of their tissue and developmental expression patterns and likely functions (from knockout data). This information will then be used as a basis for studying the evolution of the more complex and diverse 30+ different MDC genes (and their associated pseudogenes) identified within mammals.

• Novel genes involved in mammalian fertility

  Recently we have adopted a series of bioinformatics approaches to identify and clone novel genes which are highly expressed and developmentally-regulated in the testis and therefore likely to play a role in sperm function. These include differential cDNA library screening approaches, as well as microarray analysis. Database searches have revealed that some of the sequences identified represent novel, testis-specific isoforms of known proteins associated with somatic cells; others show no similarity to known proteins and therefore are likely to have novel functions. The aim of this project will be to use a variety of molecular genetic and cell biology approaches to further characterise one or more of these testis-specific genes in an attempt to establish their precise function.

• Group

  Abby Taylor, Ben Richardson, Kate Heesom.

  Recent publications

  Frayne, J., Hurd, E.A., and Hall, L. (2002) Human tMDC III: a sperm membrane protein with a potential role in oocyte recognition. Human Reproduction 8, 817-822.

  Frayne, J. and Hall, L. (2002) A re-evaluation of sperm protein 17 (Sp17) indicates a regulatory role in an A-kinase anchoring protein complex, rather than a unique role in sperm-zona pellucida binding. Reproduction 124 767-774.

  McLaughlin EA, Frayne J, Bloomerg G, Hall L.. (2001) Do fertilin beta and cyritestin play a major role in mammalian sperm--oolemma interactions? A critical re-evaluation of the use of peptide mimics in identifying specific oocyte recognition protiens. Molecular Human Reproduction 7 313-317

  Hall, L. and Frayne, J. (1999) Non-functional fertility genes in humans: contributory factors in reduced male fertility? Human Fertility 2 36-41.