RESEARCH PROFILE

Research Interests: Parturition in mammalian species, uterine physiology, microgenomics, molecular basis of electrogenesis in smooth muscle, mathematical biology. Summary:Rises in intracellular calcium are essential for contraction in myometrial smooth muscle. Calcium is not only an important second messenger for the generation of force via myosin light chain kinase, but also depolarizes the plasma membrane allowing for activation of other voltage dependent ion channels. This voltage dependent control of excitability is modulated in a gestation dependent manner in all mammalian species such that as gestation progresses the myometrium becomes increasingly excitable. These biophysical changes are mediated by alterations in ion channels, pumps, agonist receptors and the sub cellular architecture of heterogeneous cell types within the uterus. In order to considered the process of activation of the uterus in its entirety there is a requirement for a combination of molecular, biophysical, and modelling techniques. In our lab we utilise patch-clamp electrophysiology, microelectrodes, calcium imaging (both confocal and light microscopy), laser capture micro-dissection, single cell RT-PCR, qRT-PCR, and conventional protein techniques such as immunohistochemistry and western blotting. Modelling the uterus: Collaborators:Warwick Systems Biology (Prof David Rand, Dr Hugo van den Berg, Dr Magnus Richardson), Manchester (Dr Michael Taggart,Dr Henggui Zhang), Leeds (Prof. Arun Holden). We are part of a multi-centre group of UK-based researchers who are developing a computational model of the human and rodent uterus. The model works on several levels, from classical Hodgkin-Huxley type modelling of time dependent active conductances in a single cell , through to coupled models of heterogeneous networks. The collaboration has assembled intial basic models of spatio-temporal patterns of excitibility mapped to the full 3D geometry of the pregnant human uterus. Our end goal is to have a computer based simulation of the pregnant human uterus to test quantitatively scientific ideas of cellular function; to model the effects of mutations in key genes; and to simulate complex phenomena in order to improve clinical treatments and diagnosis e.g. improved understanding of clinical EHG data.

CURRENT RESEARCH PROJECTS

• MRC Capacity Building Studentships., with Singer, Donald, Clinical Sciences Research Institute, Rand D A, Blanks A M, Shmygol A. Mathematics, Clinical Sciences Research Institute, MRC, Project Start Date: 01/10/2008 Project End Date: 30/09/2012
  
  

  Further Research Projects

SELECTED PUBLICATIONS

• Blanks A M, Zhao Z, Shmygol A, Bru-Mercier G, Astle S, Thornton S (2007) 'Characterization of the molecular and electrophysiological properties of the T-Type calcium channel in human myometrium.' Journal Of Physiology 581 (3), 915 - 926 (0022-3751) [article]
• Taggart, M.J. (2007) 'Towards understanding the myometrial physiome: approaches for the construction of a virtual physiological uterus' BMC Pregnancy and Childbirth 7 (1), (1471-2393) [article]
• Shmygol A, Blanks AM, Bru-Mercier G, Gullam JE, Thornton S. (2007) 'Control of uterine Ca2+ by membrane voltage: towards understanding the excitation-contraction coupling in human myometrium.' Annals Of The New York Academy Of Sciences 1101 97 - 109 (0077-8923) [article]
• Blanks A., M., & Thornton S. (2007) 'Gene redundancy: Lessons for Tocolysis?' in Preterm Birth: Mechanisms, Mediators, Prediction & Interventions., Editors: Petraglia, F., Strauss, J.,F., Gabbe,S.,G., & Weiss, G. (9780415392273), Informa
• Shmygol, A., Gullam, J., Blanks, A., M., & Thornton, S. (2006) 'Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility.' Acta Pharmacologica Sinica 27 (7), 827 - 832 (1671-4083)

Further Publications

Conference Papers