The Alexander Silberman Institute of Life Science

Membrane traffic in health and disease (endocytosis, exocytosis, transcytosis); Membrane domains; Epithelial cell polarity; Cell biology of enteric bacterial pathogens; Pathogenic bacteria – epithelial host interactions; Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) 

The mechanism of exocytosis; Neurodegeneration: Development of drugs for Parkinson’s and Alzheimer’s disorders.

The past decade has witnessed a paradigm shift in brain research. A transition from a dogmatic brain-focused approach toward a holistic conception of health that integrates key signaling hubs of the human body—such as the gut and its microbial populations, the peripheral immune system, and other mucosal barrier surfaces—is increasingly acknowledged as necessary to understand and cure neurological disorders, such as Alzheimer’s disease, stroke and brain tumors. We investigate the physiological connections between the digestive, immune and nervous systems in a holistic approach, allowing better understanding of neurological diseases in the context of aging. We study how processes which take place in the gut, affect brain functions in health and disease, and looking at the whole-organism level to identify novel targets to treat brain pathologies.

Biophysics Cell-matrix interactions in directing cell-fate decision making, Remodeling of the nuclear matrix of lamins and chromatin

Molecular basis of iron disorders, mapping of iron in cells and tissues, diagnosis and treatment of iron overload and diseases of iron accumulation.

Read more:

• THE VALUE AND PRICE OF MEN’S ADDICTION TO IRON - On chronic iron deficiency and novel treatments relevant to corona days 
• IRON THE METAL OF LIFE AND DEATH
• SERIES OF LECTURES ON THE  BREAKTHROUGHS IN LIFE SCIENCES AND MEDICINE

Watch the following videos:

• Human iron economy in health and disease" 
• “The ironic role of diagnostic tests in saving humans in times of plague"

Development of constitutively active MAP/stress kinases for studies of the etiology cancer and inflammation. Revealing the mechanism of gene expression under stress in yeast and mammalian cells. Focusing on Gcn4, Hsf1 and Msn2/4. Analysis expression of stress-related genes in oncogenically-transformed cells.

Biochemistry, physiology and biophysics of red blood cell and malarial parasite membranes. Biochemistry and physiology of energy and oxidative metabolism of malarial parasites. Mode of antimalarial action of quinoline containing drugs and the molecular basis of drug resistance. Development of new antimalarial drugs. Mathematical modeling of the chemotherapy of malaria.

Structural biology of large protein complexes. Mass-spectrometry. Computational structural modeling based on multiple information sources. Protein structure prediction.

Function of ubiquitin in eukaryotic cells: its role in intracellular proteolysis, stress and DNA repair. Protein degradation signals in eukaryotic cells.

1. Pre-genetic mechanisms promoting development of bacterial resistance to antibiotics
2. Characterization of oligomers of the alpha-Synuclein protein as factors in the development of Parkinson's disease
3. Allosteric signal transmission through DNA
4. Method development  for structural characterization of proteins in Vivo

Signal transduction, Signal transduction therapy,Cancer Research, Medicinal Chemistry.

The dynamic processes of nerve terminals and the molecular aspects of synapse functioning. Control of exocytosis in regulated secretory systems. Differentiation and neurotransmitter phenotype acquisition in neurons, a study by proteomics and genomics approaches. Bioinformatics. Large scale studies of biological sequences and their global organization. Proteomics. Structural genomics.

• To unravel how bacterial pathogens manipulate host physiology and drive immune responses to change the intestinal environment, overcome the competition of the microbiota, expand, and transmit to the next host. 
• To understand how intestinal inflammatory diseases initiate and progress, and how intestinal homeostasis is maintained and regulated.  

• Manipulating the pathogen (using bacterial genetics and bacteriology techniques).
• Analyzing host responses (using different genetic mouse models, drugs, dietary interventions, etc.).
• Controlling the microbiota (using germ-free mice, defined microbial communities, and microbial community analysis).  

Structural determination of biologically related macromolecules via X-ray crystallographic techniques. Ligand recognition, initial signaling events, and the role of dimer/oligomer orientation in cytokine receptor systems. Structural studies of avidin/streptavidin - biotin high affinity systems. Structural based drug design and optimization. Combinatorial approaches in drug discovery.

Translocation of proteins and nucleic acid across the nuclear envelope of animal and plant cells. Entry of viral genome into nuclei of infected cells, isolation and characterization of plant cells cytosolic receptors required for nuclei import, the use of specific synthetic peptides to block nuclear import of proteins and nucleic acids, as a way to inhibit viral infection.

1. Transcriptional control of genes involved in sex steroid synthesis in the gonads and placenta.
2. Proteolysis and protein quality control during mitochondria organellogenesis in steroidogenic cells.

Molecular membrane biology, structure biology, bioenergetics, biochemistry, biophysics.

Chromatin biology, Epigenomic mechanisms, Cellular differentiation, Cellular heterogeneity, single cell technology

High throughput analysis of signals that trigger misfolded protein elimination and the contribution of cellular chaperones. 

System biology of redox regulation, intrinsically disordered chaperones, computational and experimental biology,proteomics and mass spectrometry.

Antibiotic resistance is a growing global public health concern and transporters are essential for the acquisition of resistance Our work calls for an integration of our view of the transporter cohort (the effluxome) in the cell and the realization that they all labour together to maintain cell homeostasis.  The process of identification of the members of the effluxome, the elucidation of the nature of the interactions and their role in cell physiology provides a fascinating challenge for the future. 

Development of computational method for redesign of protein-protein interfaces for altered affinity and binding specificity. the projects include redesign of calmodulin-target interactions, AChE-toxin interactions, Ras-effector interactions, and prion protein interactions.

Stress responses. Antisense technology. Acetylcholinesterase biology. Molecular neurobiology. Messenger RNA studies

Channels, Carriers and Pumps