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Raine Visiting Professor Lecture Series Professor Michael Raghunath Deputy Head for Research, Division of Bioenginnering Chair, Graduate Programme in Bioengineering National University of Singapore will present a Raine Lecture entitled: The power of the excluded volume effect in biology – putting the genie back into the bottle (Abstract overleaf) on Tuesday, 15th July 2008 at 1.00pm School of Anatomy and Human Biology 1st Floor, Seminar Room (1.81) All welcome Michael Raghunath received his MD from Mainz University, Germany, in 1987 and completed training in immunopathology in 1990 at the University of Heidelberg. He became involved in matrix biology and wound healing as a postdoctoral scientist at the University Children’s Hospital in Zurich. In 1997 he was appointed private docent (Lecturer) with a PhD (habilitation) for Physiological Chemistry and Pathobiochemistry at the University of Muenster, Germany where he also received clinical training in dermatology. In 2000 Dr Raghunath joined Dr. Suwelack at Skin and Health Care AG as R&D Director to position the company for the wound care market. In 2002 Dr Raghunath returned to the Department of Dermatology, Muenster, and in 2003 he joined the National University of Singapore as an Associate Professor, jointly appointed between the Division of Bioengineering (Faculty of Engineering) and the Department of Biochemistry (Yong Loo Lin School of Medicine). In 2005 he was appointed Deputy Head for Research at the Division of Bioengineering and Chair of the Graduate Programme in Bioengineering in the NUS Graduate School of Integrative Sciences and Engineering. Professor Raghunath’s experience spans more than 20 years in the field of matrix biology (pathobiochemistry of collagens and elastic microfibrils) and skin biology (wound repair, cornification disorders). His Tissue Modulation Laboratory (www.tissuemodulation.com) pursues research on antifibrosis with the aim of interfering with the fibrotic pathway at epigenetic and protein level. To this end, his group has developed a novel drug discovery tool, the Scar in a Jar. A second research line is derived from the angiogenic side effects of prolyl hydroxylase inhibitors, an antifibrotic compound class. Derived from earlier work on the crosslinking enzyme transglutaminase a biological tissue glue is currently being developed. Epigenetic modifications as biomarkers and tools for tissue engineering are also being pursued using human mesenchymal and embryonic stem cells. Finally, as an overarching theme, the application of macromolecular crowding in biotechnology is rolled out on a broad scale. University Host: Professor Miranda Grounds School of Anatomy and Human Biology [email protected] 6488 3486 Lyn Ellis Raine Medical Research Foundation [email protected] Telephone: (08) 9386 9880 Abstract Michael Raghunath Raine Lecture 15 July 2008, UWA, Perth The power of the excluded volume effect in biology - putting the genie back into the bottle If anyone of us was to develop a gross disproportion between cell mass and surrounding water we would be rushed to the emergency unit and somebody would talk to us about “oedema” or “effusion”. However, we are quite ignorant about the same situation in contemporary cell culture: very thin layer of cells are bathed in oceans of aqueous culture medium. This artificial setting leads to the dilution of signalling molecules and the dispersion of reaction partners that would better be more closely together. The same unphysiological situation is present in enzymatically driven procedures which are made to happen in cuvettes and tubes that contain aqueous salt solution – and nothing much more. However, if we look into a tissue and zoom into the microscopic scale we find the interior and the exterior of cells crowded with macromolecules leaving only confined pockets where other molecules (f.e. enzymes) can exert their functions and initiate or sustain biological processes. Macromolecular crowding and its resultant excluded volume effect is possibly one of the most important drivers of biochemical processes on the nanoscale. Employing this principle and trying to put the genie back into the bottle, we have been able to accelerate enzymatically driven key steps in the deposition of a collagen extracellular matrix dramatically. Using a much cleaner system like polymerase chain reaction, reverse transcription, or restriction digests we have been able to achieve dramatic improvement on a whole scale of parameters. Finally, we also found that macromolecular crowding improves and accelerates differentiation of human mesenchymal stem cells, presumably by rearranging lipid rafts on the cell membrane.