EMBO Cancer Young Investigator Program 2010
Split, Medils 14-16 Jun, 2010
We are pleased to announce the first EMBO Cancer YIP meeting in Mediterranean Institute for Life Science located in Split, Croatia. Meeting organizers are Eric So and Jesus Gil.
Challenges in biomolecular simulation:
On comparing simulated with experimental data
Monday, 30.03.2009., 4 pm, large lecture hall at MedILS
Boris Kablar, M.D., Ph.D.
Associate Professor
Dalhousie University
School of Medicine
Department of Anatomy and Neurobiology
5850 College Street
Halifax, NS B3H 1X5
Canada
Since July 2000, the members of the Mouse Models of Human Diseases Laboratory have been able to study the role of muscle in the epigenetic shaping of developing tissues and organs employing an approach based on mouse mutagenesis and pathology. Muscle tissue is one of the four basic tissue types that the body is consisted of. There are three types of muscle tissue and we are interested in one of them, the skeletal or striated muscle. We can study the developmental role of muscle in the whole mouse embryo or fetus, because it is enough to knock out two myogenic regulatory factors (MRFs), Myf5 and MyoD, to obtain an embryo without any skeletal musculature. Obviously, such a fetus cannot survive after birth, but it is viable as long as it is in the womb.
Even though it is understandable that the muscle may have numerous functions during development, we think of muscle as either an executor of various movements or as a provider of neurotrophic factors. Therefore, I will concentrate on the description of two major research programs performed in this laboratory:
The first one, also known as developmental morphodynamics, deals with studies that examine the ability of muscle to provide mechanical cues for organogenesis. In this program, we are trying to understand mechanical control of tissue morphogenesis during development. In fact, the analysis of Myf5:MyoD compound nulls reveals that several organs have difficulties to fully develop in the absence of the musculature. Organs that depend on continuity between pre- and post-natal motility are: lung, retina, inner ear and some parts of the skeleton (e.g., mandible, clavicle, sternum and palate). Diseases or phenomena that are modeled in this research program include: pulmonary hypoplasia, motion vision, angular acceleration, cleft palate and sternum, temporomandibular and acromioclavicular joint agenesis.
The second research program is composed of experiments that test the neurotrophic hypothesis. In this program, we are trying to find out if there is a muscle-provided trigger of motor neuron death ultimately relevant to the motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The main reason for this kind of thinking is the fact that a complete absence of lower and upper motor neurons, which is the pathological definition of ALS, is only achieved in the complete absence of the muscle.
Mutual embryonic inductive interactions between different tissue types and organs, between individual cell types belonging to the same or different lineages, and between various kinds of molecular players, are only some examples of the complex machinery that operates to connect genotype and phenotype. Our studies so far indicate that some aspects of this interplay can indeed be studied as proposed, confirming the role of skeletal muscle contractile and secretory activity in the epigenetic shaping of organs, tissues and cell fate choices. We will continue this analysis to gain more insight into the nature of the epigenetic events that lead into the emergent properties of a phenotype.
Role of skeletal muscle in the epigenetic shaping of organs, tissues and cell fate choices
Daniela Kruschel, Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland and MedILS, Split
Thursday, 05.02.2009., 4 pm, MedILS lecture hall
Group II introns, which are ribozymes originating from organellar genes of plants, fungi, lower eukaryotes and many bacteria, have the ability to self-splice out of the primary RNA transcript. In addition, they can reinsert themselves into RNA and DNA, and are therefore mobile genetic elements. Metal ions are thereby strictly required for folding and catalysis. These introns consist of a conserved set of six domains (D1-D6) which are defined by characteristic secondary structural elements. D1 is not only the largest of the six domains but in addition recognizes the intron through base-pairing of two regions in D1, the exon binding sites 1 and 2 (EBS1 and EBS2) with the two intron binding sites (IBS1 and IBS2) located at the end of the 5’-exon. In this study, we used NMR spectroscopy to investigate the structural and metal ion requirements on the formation of the 5’-splice site of the group II intron ai5γ located in the cox1 gene of Saccharomyces cerevisiae. The solution structure of the system comprising the hairpin with EBS1 located in the loop was solved in the absence and presence of IBS1. Bound to IBS1, EBS1 adopts a novel conformation, which is specifically stabilized by divalent metal ions. Our results provide an important basis for an understanding of the structure and function of the splice site at atomic resolution.
The Effect of Metal Ions on Splice Site Formation of Group II Intron Ribozymes
Daniela Kruschel, Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland, and MedILS, Split
Talk by Anton Polyansky “Peptides in membranes. Application of molecular modeling techniques”
Peptides in membranes. Application of molecular modeling techniques
talk by Anton Polyansky, of the Laboratory of Biomolecular Modeling at the Russian Academy of Sciences
November 20th 2008, 4 pm, large lecture hall at MedILS
Natural substances may interact with numerous target proteins in human cells. For the flavonoid quercetin a method has been developed which allows the identification of unknown target proteins. The target proteins that have been of particular interest to us include the cytoskeletal proteins actin and tubulin and their associated motor proteins. New inhibitors for these proteins have been identified and the effect of the inhibitors studied in various cellular test systems. Possible medical applications will be discussed.
Interaction of natural substances with cellular target proteins (prof. dr. Herwig Gutzeit, TU Dresden, Germany)
October 9th 2008, 10 am, large lecture hall at MedILS
Skeletogenesis and hematopoietic development (prof. dr. Leonardo Aguila, University of Connecticut Health Center, USA)
07.10.2008, 9 am, MedILS, large lecture hall
The phenomenon referred as «mucilage of Northern Adriatic» has been observed infrequently over the past three centuries but more recently its intensity and frequency of occurrence has increased dramatically. The phenomenon manifests itself in rapid production of enormous amounts of gelatinous matter in the water column and covering the sea surface at a scale observable from the satellite. The mucilage phenomenon has attracted attention of many scientists worldwide and research is performed by oceanographers, biologists and chemists. Current views leave no doubt on phytosynthetic production of long chain polysaccharide molecules by unicellular marine algae, as a proximal source constituting the gel network, but the basic mechanism of mucilage events is still not understood.
Studies of supramolecular organization of organic molecules in seawater into vesicles and microgels have revealed that the macroscopic phenomena, such as mucilage events are governed by biological and abiotic transformations at the micro- and nano- scales.
Discovery of AFM (Atomic Force Microscopy) has made possible the masurements of atomic forces for imaging living and non-living organic structures at molecular and sub-molecular resolution under ambient conditions.
I shall describe here how we applied AFM imaging to reveal the process of marine gel formation at the nanoscale, starting from extracellular production of polysaccharide chains by a living diatom cell, to gradual and multiple entanglement of polysaccharide molecules into the polysaccharide gel networks which reached macroscopic dimensions during the mucilage event.
Mucilage phenomenon at the nanoscale (dr. Vesna Svetličić, Institute Ruđer Bošković, Zagreb)
Why our proteins have to die so we shall live
A lecture for the general public
Aaron Ciechanover, Nobel Prize winner
Cancer and Vascular Biology Research Center, Faculty of Medicine,
Technion-Israel Institute of Technology, Haifa, Israel
Faculty of Economics, Split, Large Amphiteather, Tuesday, September 16th 2008, 6pm
Proteins are the machines that drive our body. They are responsible for all our activities such as walking, seeing, hearing, heart beeping, digestion, respiration, secretion of waste materials. Unlike the items that surround us and that we use daily, like furniture and our clothes, the body proteins are in a dynamic state, they are being destroyed and renewed all the time and in an extensive manner. We are destroying daily up to 10% of our proteins and generating new ones instead. The obvious questions are (i) why this occurs, (ii) what is the mechanism that carries out this function, (iii) what are the diseases that result if the mechanism does not work properly, and (iv) how can we cure these disease. In the lecture we shall try to shed light on these problems, and understand the value of basic research for the development of drugs to target many diseases that affect us in the Western world - cancer and neurodegenerative disorders like Alzheimer’s disease, for example. No doubt research of the system will yield practical implications to diseases of the developing world as well – infectious diseases, for example, but researchers need proper investment to explore these new venues.
Why our proteins have to die so we shall live (Aaron Ciechanover, Nobel Prize winner, Technion, Israel)
The Ubiquitin Proteolytic System: From Basic Mechanisms through Human Diseases and onto Drug Targeting (Aaron Ciechanover, Nobel Prize winner, Technion, Israel)