Newcastle University

Research Interests

Reproductive Cell Biology

A central focus of our research concerns the mechanisms that regulate chromosome segregation during oogenesis. Oogenesis comprises a highly regulated series of differentiation steps in which diploid progenitors are programmed to become haploid and to regain the potential for pluripotency. This extraordinary transition occurs during meiosis and involves structural rearrangement of chromosomes; remodelling of telomeres, centromeres, and chromosome-associated proteins. Elucidating the mechanisms that regulate these processes is key to understanding the mechanisms that regulate embryonic stem cell behaviour, and to realising the therapeutic potential of somatic cell nuclear transfer.

We are using mouse and human oocytes to investigate cell cycle regulation during meiosis. Our results indicate that chromosome segregation in female meiosis requires critical functional modifications of a number of cell cycle regulators. We are currently addressing two important questions 1) How does the chromatin of a somatic cell (which has not been exposed to the remodelling events of meiotic prophase) interact with the meiotic regulatory milieu? 2) What is the mechanistic link between female reproductive senescence and aberrant chromosome segregation in oocytes? The latter is a collaborative project with Professor Tom Kirkwood, Institute of Ageing and Health.

In an extension of our interests in cell cycle regulation, we have recently embarked on a project to decipher the mechanisms regulating proliferation and genome surveillance during self-renewal of human embryonic stem (ES) cells. We are also working towards the production of clinical grade ES cells. This is a collaborative project with Professor Roger Pedersen’s group, Cambridge and Professor Alison Murdoch, Newcastle Fertility Centre. We are also developing a GMP-compliant bio-processing system designed to optimise environmental conditions for ES cell derivation and nuclear transfer.

In collaboration with Professor Doug Turnbull, Institute of Neurosciences, we are investigating the mechanisms regulating replication and segregation of mitochondrial DNA in oocytes and early embryos. A translational application of this work is to optimise pronuclear transfer techniques in human zygotes with the ultimate aim of developing IVF-based strategies to prevent transmission of mitochondrial DNA mutations from mother to child.

Key Publications

Herbert M, Levasseur M, Homer H, Yallop K, Murdoch A, McDougall A (2003) Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1. Nat Cell Biol 5:1023-1025

Homer HA, McDougall A, Levasseur M, Yallop K, Murdoch AP, Herbert M (2005) Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes. Genes Dev 19:202-207

Brown DT, Herbert M, Lamb VK, Chinnery PF, Taylor RW, Lightowlers RN, et al. (2006) Transmission of mitochondrial DNA disorders: possibilities for the future. Lancet 368:87-89

Co-workers

Lyndsey Craven BSc
Muscular Dystrophy Campaign PhD Student
Linda Ferguson BSc
ONE NorthEast Technician
Louise Hyslop PhD
ONE NorthEast Research Associate
Lisa Lister BSc
MRC Junior Research Associate
Gareth Greggains BSc
Spitzer Foundation PhD Student
Sarah Pace BSc
Infertility Research Trust PhD Student
Rez Prathalingam PhD
ONE NorthEast Research Associate

• Hyslop L, Prathalingam N, Nowak L, Fenwick J, Harbottle S, Byerley S, Rhodes J, Watson B, Henderson R, Murdoch A, Herbert M. A Novel Isolator-Based System Promotes Viability of Human Embryos during Laboratory Processing. PLoS ONE 2012, 7(2), e31010.
• Choudhary M, Nesbitt M, Burgess L, Hyslop L, Herbert M, Murdoch A. Egg Sharing for Research: A Successful Outcome for Patients and Researchers. Cell Stem Cell 2012, 10(3), 239-240.
• Prathalingam N, Ferguson L, Young L, Lietz G, Oldershaw R, Healy L, Craig A, Lister H, Binaykia R, Sheth R, Murdoch A, Herbert M. Production and validation of a good manufacturing practice grade human fibroblast line for supporting human embryonic stem cell derivation and culture. Stem Cell Research and Therapy 2012, 3(2), 12.
• Irving L, Alston C, Craven L, Herbert M, Turnbull DM. Analysis of mitochondrial DNA mutant loads in oocytes & preimplantation embryos for the 14709T > C & 14487T > C mtDNA mutations by pyrosequencing. In: Neuromuscular Disorders: United Kingdom Neuromuscular Translational Research Conference. 2011, London, UK: Elsevier Ltd.
• Craven L, Elson JL, Irving L, Tuppen HA, Lister LM, Greggains GD, Byerley S, Murdoch AP, Herbert M, Turnbull D. Mitochondrial DNA disease: new options for prevention. Human Molecular Genetics 2011, 20(R2), R168-R174.
• Lister LM, Kouznetsova A, Hyslop LA, Kalleas D, Pace SL, Barel JC, Nathan A, Floros V, Adelfalk C, Watanabe Y, Jessberger R, Kirkwood TB, Hoog C, Herbert M. Age-Related Meiotic Segregation Errors in Mammalian Oocytes Are Preceded by Depletion of Cohesin and Sgo2. Current Biology 2010, 20(17), 1511-1521.
• Santos F, Hyslop L, Stojkovic P, Leary C, Murdoch A, Reik W, Stojkovic M, Herbert M, Dean W. Evaluation of epigenetic marks in human embryos derived from IVF and ICSI. Human Reproduction 2010, 25(9), 2387-2395.
• Herbert M, Fenwick J, Harbottle S, Walker J. Laboratory Apparatus with Incubator. UK: NHS Innovations, 12/083996, 18/11/2010.
• Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 2010, 465(7294), 82-85.
• Kouznetsova A, Lister L, Nordenskjold M, Herbert M, Hoog C. Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice. Nature Genetics 2007, 39(8), 966-968.
• Brown D, Herbert M, Lamb V, Chinnery PF, Taylor R, Lightowlers R, Craven L, Cree L, Gardner JL, Turnbull DM. Transmission of mitochondrial DNA disorders: possibilities for the future. Lancet 2006, 368(9529), 87-89.
• Homer HA, McDougall A, Levasseur M, Murdoch AP, Herbert M. Mad2 is required for inhibiting securin and cyclin B degradation following spindle depolymerisation in meiosis I mouse oocytes. Reproduction 2005, 130(6), 829-843.
• Homer HA, McDougall A, Levasseur M, Yallop K, Murdoch AP, Herbert M. Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes. Genes and Development 2005, 19(2), 202-207.
• Homer HA, McDougall A, Levasseur M, Herbert M. Restaging the spindle assembly checkpoint in female mammalian meiosis I. Cell Cycle 2005, 4(5), 650-653.
• Herbert M, Levasseur M, Homer H, Yallop K, Murdoch A, McDougall A. Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1. Nature Cell Biology 2003, 5(11), 1023-1025.
• Fenwick J, Platteau P, Murdoch AP, Herbert M. Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro. Human Reproduction 2002, 17(2), 407-412.
• Griffiths TA, Murdoch AP, Herbert M. Embryonic development in vitro is compromised by the ICSI procedure. Human Reproduction 2000, 15(7), 1592-1596.
• Herbert M, Morgan J, Levasseur M, Murdoch AP, McDougall A. A non-degradable form of cyclin can be used to induce arrest at the first meiotic metaphase in human oocytes. In: ESHRE campus workshop 'ART in the year 2000'. 1999, Hamburg-Norderstedt, Germany: Oxford University Press.
• Evbuomwan IO, Fenwick JD, Shiels R, Herbert M, Murdoch AP. Severe ovarian hyperstimulation syndrome following salvage of empty follicle syndrome. Human Reproduction 1999, 14(7), 1707-1709.
• Clouston,H.J., Fenwick,J., Webb,A.L., Herbert,M. Murdoch,A.P., Wolstenholme,J. Detection of mosaic and non-mosaic chromosome abnormalities in 6-8 day old human blastocysts. Human Genetics 1997, 101, 30-36.