Research Group of Professor Lorraine Young, University of Nottingham

Research Group of Professor Lorraine Young, University of Nottingham

Professor Lorraine Young is Director of the newly formed Wolfson Centre of Stem Cells, Tissue Engineering and Modelling (STEM) at the University of Nottingham. Her work on the epigenetic remodelling of sperm and oocytes into the preimplantation embryo has led to an interest in human embryonic stem cells as a novel model for human development.

Lorraine’s team investigates how, at the epigenetic level, cells acquire totipotency during normal embryonic development. Combined with the ongoing investigation of the nature of the epigenetic reprogramming events a cell undergoes in an oocyte cytoplasm after somatic cell nuclear transfer, an exciting application of this work is to develop directed cellular transdifferentation ex ovo for the production of autologous stem cells. Another main focus is in the epigenetic evaluation of human embryonic stem cells (hESC) and their derivatives, a vital pre-requisite for regenerative medicine applications. Since epigenetic disruptions in the embryo are likely to be transmitted to embryonic stem cells, tumorigenic potential or altered differentiation capacity may be inherent to derivatives. The team is focusing on changes in DNA methylation, part of the regulatory process that acts to stably silence transcription over many cell generations. A major application of human embryonic stem cells in Nottingham is to develop novel models for human disease. The laboratory is particularly interested in the predisposition of adult cardiovascular disease by maternal nutrition, otherwise known as “the developmental origins of adult disease”. They are investigating the hypothesis that nutrients which determine intracellular methyl group availability, such as folate, vitamin B12 and methionine, can affect DNA methylation at specific loci in the embryo or fetus and programme development by altering cellular proliferation or differentiation in specific tissues. Human embryonic stem cells provide a unique system to model early embryonic and later cardiac development and how these processes are affected by specific nutrients.

In addition to maternal nutrition, Lorraine’s group are investigating the effects of embryo technologies, such as in vitro fertilisation and embryo culture on developmental programming by epigenetic changes in the preimplantation embryo. Phenotypic consequences (including Large Offspring syndrome) can arise in the fetus, after birth or in embryo-derived stem cells. Current and recent work in the laboratory has been funded by BBSRC, Royal Society, British Council, NIH and University of Nottingham.

Lorraine studied for her BSc and PhD degrees at the University of Aberdeen. She then undertook postdoctoral research at the University of Liverpool and the Roslin Institute in Edinburgh, where she worked with the team that cloned Dolly the sheep. Developmental problems with cloned animals led Lorraine to uncover problems with epigenetic reprogramming that developed into a broader interest in developmental epigenetics. Lorraine joined the University of Nottingham as a Lecturer in the School of Human Development in 2001 and was promoted to Chair (Professor of Molecular Embryology) in 2006. She has recently moved into Nottingham’s flagship Centre for Biomolecular Sciences where she is very excited about the new multidisciplinary opportunities yielded by the creation of STEM. The world’s first MSc degree in Stem Cell Technology will be run by STEM from October 2007 (www.nottingham.ac.uk/human-development/PGCOURSES/), providing 16 students each year from across the globe training in stem cell imaging.

The purpose build laboratories within STEM have a state of the art imaging suite, largely set up as a collaboration between Chris Wood of Improvision and Lorraine’s very motivated PhD student, Emma Lucas. One of Emma’s images of the preimplantation embryo, from which human embryonic stem cells are derived, is featured below. For the past four years the group have been using Openlab and Volocity. Following their recent laboratory move and the purchase of a new microscope, the group have now upgraded their Volocity software to include the Acquisition and Restoration products. This has enabled them to image their sensitive samples more quickly and with less bleaching compared to using a laser scanning confocal microscope, applying deconvolution post-acquisition.

Emma says "Using a wide variety of tissue types, such as monolayer cells, histological sections and preimplantation embryos, as well as an assortment of different detection methods, means that all the users in our lab require something different from our imaging software. The user-friendly interface and flexible nature of Improvision software means that everyone can easily acquire and analyse their data, and is helping us to get the most information from our samples." Lorraine adds “Volocity is helping us unlock the secrets of embryonic cells”.

Please visit Lorraine's website for further information about her work.

 

The image shows a mouse blastocyst (the stage of embryonic development from which embryonic stem cells are derived), using FITC immunostaining to reveal the pattern of DNA methylation (5-methylcytosine distribution) in the cells. Using Volocity Acquisition to control a Nikon 90i microscope, a Z-series was captured and subsequently deconvolved using Volocity Restoration to give a 3D image of DNA methylation in the embryo, allowing visualisation of both the inner cell mass and trophectoderm cell layers.