Download The power of the excluded volume effect in biology

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.