Research groups

Jan Frayne
Senior Lecturer

+44 (0)117 33 12127 (tel)
+44 (0)117 33 12168 (fax)
jan.frayne@bristol.ac.uk

Research

My research group focuses on two discrete research areas:

• in vitro erythropoiesis from stem cells sources in collaboration with NHSBT to define the molecular regulation of this process with the aim of generating human red blood cells with therapeutic potential
• sperm maturation and function to increase our understanding of male fertility, as well as to develop novel contraceptive strategies.

Recent progress in the field of stem cell research raises the possibility that therapeutic quantities of blood cells could be obtained from cultures of haemopoietic stem cells in vitro. However, erythropoiesis is regulated by myriad factors via intracellular signal transduction pathways and the molecular mechanisms regulating this process are far from delineated. In collaboration with Prof Dave Anstees research group (at the Bristol Institute for Transfusion Sciences) we are using a range of innovative proteomic technologies and biochemical approaches to define the molecular regulation of erythropoiesis in vitro and hence develop systems to generate mature red blood cells from stem cell sources (fig 1). We are also investigating the function and role of the erythropoietic specfic transcription factor, EKLF, in the differentiation of human stem cells during erythropoiesis along with its role in the generation of red blood cell disorders.

Mammalian spermatozoa released from the testis have to undergo a series of complex maturational processes and molecular modifications that ultimately lead to the acquisition of motility and fertilising competence. However, although essential for reproductive success, such processes are poorly defined at the molecular level. One such essential event is a process called capacitation that occurs in the oviduct and which is characterised by a switch in the swimming pattern of sperm from forward progressive to hyperactivated motility, along with a marked increase in the phosphorylation of flagellar proteins that undoubtedly link to the change in swimming pattern. However, although critical for fertilisation the intracellular pathways involved and the regulation of capacitation is very poorly understood.

We are currently investigating the signal transduction pathways involved in this process. We have established an in vitro system for sperm capacitation (fig 2) and have identified novel forms of kinases which we are presently further characterising.

In addition we are studying the role and activity of other essential sperm proteins including GPX5; a novel selenium-independent glutathione peroxidase proposed to play a role in sperm protection and GAPDH-2; a sperm-specific isoform of glyceraldehyde-3-phosphate dehydrogenase and putative contraceptive target.

Group

Dr Marieangela Wilson, Winnie Lau, Kongtana (Tom) Trakarnsanga

Recent publications

Jan Frayne, Abby Taylor, Gus Cameron, and Andrea T. Hadfield (2009). Structure of Insoluble Rat Sperm Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) via Heterotetramer Formation with Escherichia coli GAPDH Reveals Target for Contraceptive Design. J. Biol Chem 284: 22703-22712. 

B.M.Richardson, K.J.Heesom, S.F.Parsons, D.J.Anstee and J.Frayne (2009). Analysis of the differential proteome of human erythroblasts during in vitro erythropoiesis by 2-D DIGE. Proteomics Clin. Appl. 2009, 3, 1123–1134 .

Brewis, I.A., van Gestel, R.A., Godella, B,M., Jones, R., Publicover, S.J., Roldan, E.R., Frayne, J. & Barrat, C.L.R. (2005) The spermatozoan at fertilisation: current understanding and future research directions. Human Fertility 8, 241-251.

Frayne, J. & 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.