Wednesday 18.01.2012 16.30
Maria Garcia (host: A. Koschak)
Vice President Kanalis Consulting, L.L.C.
Kanalis Consulting, L.L.C.
Edison, New Jersey 08820 USA
"Discovery of novel, small molecule, ion channel modulators"
Friday 20.01.2012 11:30
Jürgen Hescheler (host: K.H. Hilber)
Institut für Neurophysiologie
Medizinische Fakultät
Klinikum der Universität Köln
"Induced Pluripotent Stem Cells and Regenerative Medicine"
Friday 10.02.2012 11:00
Sascha Martens (Host: Martin Hohenegger)
Max F. Perutz Laboratories
University of Vienna
Vienna Biocenter
Dr. Bohr-Gasse 9/3
A-1030 Vienna, Austria
"Molecular Mechanisms of Autophagosome Formation"
Maria Garcia (mlgarciagarcia@optonline.net)
Drug development is a long, tedious, and costly process associated with a high failure rate. The key to later success in the clinic depends on early target validation in preclinical animal species, and the nature of the chemical leads. Ion channels regulate many physiological functions, and represent the targets of certain drugs used to treat a number of pathophysiological conditions. These drugs, however, were identified and developed using whole integrated physiological read-outs in animal models of the respective disease. Human genome sequencing has identified over 400 genes that code for ion channels. In addition, native ion channels are usually made up by the functional association of identical or closely related subunits, resulting in a large number of potential targets for drug development. The question that follows is which of these targets are relevant for treating a disease condition, and very importantly, which targets have to be avoided to prevent unwanted side effects. There are a number of approaches that can be used for identifying targets of therapeutic interest, such as knowledge of a system’s physiology, use of pharmacological reagents, and very importantly, information derived from human genetics. In addition, ion channel assay technologies have significantly evolved during the last few years affording platforms that can support the screening of large chemical libraries (> 1 M compounds) in a short period of time (1-2 weeks), in order to identify leads with appropriate potency and selectivity that can be optimized by Medicinal Chemistry into a clinical development candidate. Examples of drug development efforts in the diabetes and cardiovascular areas will be discussed.
Jürgen Hescheler (j.hescheler@uni-koeln.de )
There is no doubt that work on stem cells will be the most promising approach
for the medicine of the 21st century and probably revolutionize the therapy of
many diseases including cardiac infarc-tion and failure, diabetes, Parkinson’s
disease, spinal cord lesion etc.
It is our aim to provide a fundamental basis to the development of new medical
treatments. Stem cell research is a broad field which requires nearly all
techniques of modern life science such as genetics, cell biology, physiology,
biochemistry, histology, etc. - but it also requires the input of experimental
surgery and bioengineering technologies.
Induced pluripotent stem (iPS) cells represent the most promising approach for
future stem cell-based tissue repair in regenerative medicine. iPS cells are
functionally highly similar to embryonic stem (ES) cells, but in addition have
the advantage of being ethically uncontroversial and obtain-able from readily
accessible autologous sources. However, although proof of principle for the
therapeutic use of iPS cells in neuronal and cardiac diseases has been shown
both at the laboratory scale and in animal models, the methods used today for
generation, cultivation, differentiation and selection still have to be
translated for their later clinical usage.
This presentation will give an overview on our recent research work on human
embryonic in com-parison with iPS cells. Starting from our basic investigations
on the physiological properties of car-diomyocytes developed from pluripotent
stem ells we have established in vitro and in vivo trans-plantation models
enabling us to systematically investigate and optimize the physiological
integration and regeneration of the diseased tissue.. Our main focus is the
cardiac infarction model. More-over, in vitro culture and expansion of stem
cells is far from optimal and needs further research in order to overcome
problems related to insufficient numbers of obtained stem cells and aging of
the obtained stem cell population.
Sascha Martens (sascha.martens@univie.ac.at)
Autophagosomes are small double membrane-bound organelles that are formed de novo during a process called autophagy. Autophagosomes mediate the bulk degradation of cytoplasmic material such as aggregated proteins, dysfunctional or surplus mitochondria and intracellular pathogens. Autophagy is conserved from yeast to human and has been shown to protect the organism from conditions such as starvation, neurodegeneration and infectious diseases. During autophagosome formation initially small, double membrane structures termed isolation membranes are formed. These isolation membranes expand and thereby gradually enclose cytoplasmic cargo. Finally, isola-tion membranes close to give rise to mature autophagosomes. After their formation autophago-somes fuse with lysosomes or vacuoles in yeast within which their inner membrane and the content are degraded. Despite their importance little is known about how cells generate autophagosomes. In order to gain insight into how the cellular machinery generates autophagosomes we aim to reconstitute this process in vitro. To this end we employ purified, fluorescently labeled proteins and giant unilamellar vesicles. We will present fascinating insights we gained using this system.