Research at the Department of Biological Chemistry focuses on molecular biochemistry of regulatory mechanisms.
Genetic dissection of visual transduction in Drosophila flies. Activators of the GTPase reaction in Ras oncogenic mutant proteins. The mechanism of catalysis of heterotrimeric G-proteins. The histological, pharmacological and clinical potency of signal transduction inhibitors, such as protein tyrosine kinase blockers (tyrphostins), ras inhibitors and colk2 blockers. These compounds are currently in advanced clinical trials as antitumor agents and for the treatment of psoriasis. The biochemical basis of the biological and pathological activities of the ras protooncogene. Study of ras-dependent transcription factors which are involved in the cellular stress response (c-Jun/Gcn4, c-Fos, Elk1, NFkB, Msn2/4).
Mechanism of Neurotransmitter Release
Neuronal presynaptic functions in mature and developing neurons. Molecular changes associated with the secretion in neuronal and exocrine systems. Molecular and electrophysiological studies of the mechanism of secretion of neurotransmitters such as adrenaline and insulin in the brain and in peripheral tissues. Relationship between ionic channels and the secretory proteins. Mechanism of secretion and specific mutations in voltage sensitive calcium channels in relation to neurological diseases such as Parkinsons's, Alzheimer's, Amyotrophic lateral sclerosis (ALS), brain ischemia ,etc. Development of new compounds aimed for the treatment of stroke and Parkinson's.
Cellular Regulatory Mechanisms and Development
Multidrug resistance in cancers. Development of an assay to measure the effectiveness of blockers of MDR1 in patients receiving such blockers in the clinic. Studies on the mechanism of P-glycoprotein, the multidrug resistance pump. Transcriptional regulation of genes for biosynthesis of steroid hormone in reproductive organs. Breakdown of steroidogenic proteins by the autonomous proteolytic systems in mammalian mitochondria. Molecular cloning of androgen-processing enzymes. The role of ubiquitin in the response of eukaryotic cells to stress. Identification of protein degradation signals in eukaryotic cells. Function of the ubiquitin/proteasome system in budding yeast: molecular basis for the specificity of selection of proteins for intracellular degradation. Molecular cloning, antisense inhibition, transgenic manipulations and biomedical implications of cholinergic functions. Structural studies on protein-RNA and DNA complexes involved in regulatory processes. The epigenetics of development, mining the genome of Caenorhabditis elegans.
Elucidation of the signal-transduction chain activating the redox-controlled protein-kinase of the photosynthetic membranes of oxygen-evolving eukaryotes. The mechanism of light-induced conformational changes of chlorophyll-protein complexes exposing phosphorylation sites to the redox-controlled protein kinase. The mechanism of light-induced turnover of proteins of the photochemical reaction center of the oxygen evolving photosystem II complex
Molecular pharmacology and physiology
Translocation of viral genome into virus infected cells: Construction of targeted vehicles; structural and functional delineation of anion transport mechanisms of animal cells in health and disease. Biochemical and physiological analysis of the interaction of the malarial parasite and host erythrocytes. Mode of action of anti-malarial drugs and the development of new drugs. Fate of heme in malaria-infected erythrocytes. Redox metabolism in infected cells. Characterization of transport systems in malaria-infected erythrocytes. Mathematical modeling of malaria chemotherapy. Iron metabolism and its implications in health and in disease (hemochromatosis, thalassemia and inflammation). Novel chelation therapies for iron overload diseases. Theoretical analysis of membrane transport; characterization and role of a novel regulatory nucleotide cyclic diguanylic acid; genetic analysis of diguanylic acid production and its role in cellulose biosynthesis, structural studies on protein-carbohydrate complexes relevant to cell-cell interactions.
Molecular and neurophysiological dissection of the mechanism underlying stress responces
In vivo, stress responces potentiate acetylcholine hydrolysis, suppress the neurophysiological excitation induced by anti-choline esterases and limit the susceptibility to seizure activity and neuronal toxicity. Prolonged stress induces delayed drug hypersensitivity and progressive deterioration of cognitive and neuromotor faculties that were demonstrated in transgenic mouse models. Antisense oligonucleotides (AS-ODNs) treatment prevents the accumulation of the stress-associated "Readthrough" acetylcholine esterase (AChE) isoform AChE-R under stress, suggesting antisense prevention of stress responses for early intervention with the cascade of events leading from variable stress insults to long-term neurological consequences. Mechanism of heat stress-induced cell cycle arrest in budding yeast.
Structure study of macromolecules by X-ray crystallography. Structural studies of avidin/streptavidin high affinity systems, catalytic properties of these proteins and avidin/streptavidin minimization by rational design. Signal stansduction in cytokine receptors; structures of various complexes of cytokine hormones with cognate and non-cognate extracellular domains of receptors. Studies of inhibition or attenuation of cytoplasmic signaling i pathway by the CIS/JAB protein family. Rational and combinatorial approach for the design of weight control drugs via structural studies of FALBP's. Conformational study of peptides and proteins by NMR methods. Bioinforamatics - Large scale studies of biological sequences and their structural and functional organization.
The Myers Skin BiochemistryLaboratory
The laboratory is engaged in control mechanisms and signalling of growth, differentiation,aging and apoptosis of epidermal and dermal skin cells. Autoimmune pemphigus antibodies inducing tissue acantholysis by apoptotic mechanism(funded by BSF). Aging of skin cells-corelation to apoptotic signalling system. The role of the multicatalytic proteasome in skin aging. Antipsoriatic drugs derived from Arab traditional plants. The role of glycation in hair shedding and acne. Cellular growth and differentiation of skin-keratinocytes; studies of pemphigus disease;
The Biotechnology Unit
The unit contains laboratory and pilot scale fermentors. It specializes in process development, development of strains of industrial microorganisms, production of cell mass, large-scale recombinant protein expression in E. coli and Pichia pastoris, production of fungal spores in submerged fermentation; downstream processing of microbial and fungal enzymes, immobilization of enzymes, biocatlyst development, biosensing, as well as optimization of secondary metabolites production.
The Heavy Equipment Unit
The unit contains major scientific equipment and serves all the Departments of the Life Sciences Institute. It also offers its services to various Biotechnological start-up companies of Jerusalem area. This unit is based on a minimal number of dedicated and highly trained technicians supervising and counseling scientists on the efficient use of the equipment. In-house maintenance is performed by a group of trained electronic and mechanical experts in minimal time and with maximal efficiency. The unit offers services of ultracentrifugation, cell separation, determination of amino acid composition, DNA and peptide synthesis, automated DNA sequencing, radioactive counting, HPLC and GC chromatographic separation, optical and fluorescent scanning, and automated phosphorimaging and x-ray film development services.
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