Department of Biological Chemistry

Eitan Bibi, Head

The scientific activities in the department of biological chemistry span several areas in the Life Sciences. The common thread is the study of the biochemistry of life and disease. Emphasis is given to the examination of proteins, whether soluble or membrane-bound, and their key biological functions and we seek a molecular understanding of their evolution, cellular interactions, structures and functions. A variety of biochemical, biophysical, structural, molecular-biological, and state of the art imaging methodologies are employed in our department. Overlapping interests and inter-group cooperations signify the spirit of our research. The department has more than 20 research groups whose activities are centered around the following foci of interest:

1. Protein science and macromolecular machines, including protein-protein interactions, protein-ligand interactions, evolution of enzymes, and understanding the composition of large complexes.
   
2. DNA and regulation of gene expression, including DNA repair, epigenetics, mechanism of transcription and biomolecular computing.
   
3. Structure, function, and biogenesis of membrane proteins, including ion channels, pumps, transporters, membrane enzymes and molecular motors.
   
4. Membranes, lipids, and organelles, including the mechanisms of protein and lipid transport, mechanism of autophagy and the role of lipids in membrane protein functions.
   
5. Signaling within and between cells, in bacteria, vertebrate, and invertebrate organisms, as well as molecular pathogenesis, nerve growth and regeneration,and cell differentiation.
   

A variety of methodologies are being utilized, with an emphasis on biochemistry, biophysics, molecular genetics, advanced light microscopy, computation methods, and structural tools (such as crystallography, atomic force microscope, mass spectrometry). Additional information can be obtained in the department's Home Page.

E. Bayer

Structural and functional aspects of the multi-enzyme cellulosome complex from cellulose-degrading bacteria.

1.  The cohesin-dockerin couple - Protein-protein interactions that mediate recognition and specificity in cellulosome assembly.

2.  Cellulose-binding domains as models for protein-sugar interactions.

3.  Bioinformatics of cellulases and cellulosome components

4.  Comparative genomics of cellulosome components.

5.  Structure determination of cellulosome components.

6.  Enzymology of cellulosomes for conversion of biomass to biofuels

7.  Designer cellulosomes - Selective engineering of chimaeric cellulosome constructs for nanotechnology.

8.  Avidin-biotin system - Mutated avidins and streptavidins

E. Bibi

Structure/function studies of the E. coli multidrug transporter, MdfA.
E. Bibi, N. Fluman and O. Tirosh

1.  The multidrug recognition pocket of MdfA (genetic and biochemical studies)

2.  3D crystallization of MdfA

3.  Mechanism of MdfA-mediated multidrug transport (proton/drug antiport)

Membrane protein biogenesis in E. coli
E. Bibi, E.S. Bochkareva, A. Kinori, D. Ben-Halevy, K. Ben-Harush, I. Noach

1.  FtsY, the essential prokaryotic SRP-receptor: biogenesis and function

2.  Membrane targeting and association of ribosomes in E. coli.

3.  Membrane targeting and association of mRNAs encoding membrane proteins

R. Dikstein

Transcriptional control in health and disease

1.  Mechanism of rapid transcriptional induction of NF-kappaB target genes

2.  The mammalian core promoter diversity

3.  Links between mammalian transcription and translation through common regulatory elements

4.  Transcriptional control of microRNA genes

5.  The role of TFIID subunits in embryonic stem cell pluripotency and self renewal

Translation initiation

1.  Unique translation initiation of mRNAs containing Translation Initiator of Short 5'UTR (TISU) elements

2.  Biological significance of TISU-mediated translation initiation

3.  Links between mammalian transcription and translation through TISU

M. Eisenbach

Sperm guidance in humans

1.  Molecular and behavioral mechanisms of sperm chemotaxis

2.  Molecular mechanism of sperm thermotaxis

Chemotaxis of bacteria

1.  Molecular mechanisms of sensing, signaling and response

2.  Molecular mechanism of function of the switch of the bacterial flagellar motor

Z. Elazar

Molecular mechanisms of autophagy

1.  Mechanism of autophagosomes biogenesis

2.  Autophagy and neurodegeneration

3.  Regulation of autophagy in yeast and mammals

Mechanism of intracellular protein trafficking

1.  Regulation of intra-Golgi protein transport

M. Fainzilber

Molecular mechanisms underlying spatial signaling within neurons and other large cells

1.  Retrograde signaling mechanisms in healthy, diseased or injured neurons.

2.  Molecular mechanisms of axonal communication and neuronal regeneration.

3.  Death signaling in neural tumors

4.  Size sensing mechanisms in neurons and other large cells.

A. Futerman

The molecular mechanisms of sphingolipid storage diseases (Gaucher, Niemann-Pick, and Tay-Sachs disease).

The regulation of ceramide synthesis

Sphingolipid signaling during neuronal development.

H. Garty

Regulation of epithelial ion transport:

1.  FXYD proteins as tissue specific regulators of the Na+/K+ ATPase.

2.  Kinases mediating hormonal regulation of epithelial ion-transport.

3.  Identification of aldosterone regulated genes involved in ionic homeostasis

S. Karlish

Crystalization and function of Na/K-ATPase.

Regulation of Na/K-ATPase by FXYD proteins.

Molecular mechanisms involved in generation of essential hypertension.

Development of isoform-selective drugs

Z. Livneh

Molecular and cellular analysis of error prone DNA repair (translesion DNA synthesis) in mammals.

1.  Principles of operation of mammalian error-prone DNA repair.

2.  Screening for novel genes involved in mammalian DNA damage tolerance.

3.  Genome-wide analysis of mammalian error-prone DNA repair.

4.  Analysis of DNA damage tolerance in mammalian chromosomes.

DNA repair biomarkers for risk assessment and early detection of cancer.

Mechanisms and regulation of DNA repair in stem cells.

DNA damage tolerance via homologous recombination repair in mammals.

U. Pick

Regulation of massive β-carotene synthesis in Dunaliella bardawil and its industrial utilization.

Cold acclimation and cold-induced proteins in Dunaliella.

Iron uptake by an algal transferrin.

Structure and function of salt-resistant proteins.

H⁺ and Na⁺ transporters in the halotolerant alga Dunaliella.

Z. Reich

Nuclear pore complex (NPC)-mediated macromolecular transport

1.  Transport mechanics, dynamics and energetics.

2.  Nuclear pore proteins: molecular and biophysical characterization.

3.  Nuclear import of exogenous DNA: implications for human gene therapy.

E. Reuveny

Structural and functional studies of ion channels in health and disease

1.  Biophysical analysis of the gating and permeation using electrophysiological approaches (patch clamp).

2.  Regulation of cellular distribution and signaling specificity by ion channels-associated proteins using biochemical approaches.

3.  Conformational dynamics of ion channels associated with activation using novel fluorescence-based measuring techniques.

4.  The role of the G protein coupled potassium channel in insulin secretion.

G. Schreiber

Protein-protein interactions, from basic biophysical understanding to protein design and structure-function relation.

1.  Rational design of faster associating and tighter binding protein complexes.

2.  Evaluation of direct and cooperative contributions towards the strength of non-covalent protein-protein interactions

3.  Structure-function studies of the interaction of interferon and its receptors, towards understanding the biophysical basis of heterogeneous receptor activation by a family of hormones.

4.  Bioinformatics of Protein-Protein interactions

Y. Shai

Membrane-protein interaction and molecular recognition within the membrane milieu. Implication to the function and structure of membrane proteins.

1.  Assembly and organization of pore forming toxins and ion channels in membranes: Studies with isolated fragments and intact proteins.

2.  Molecular mechanism of membrane fusion and its inhibition: Studies with HIV and Sendai Virus.

3.  Molecular basis for cell selectivity by cytolytic antimicrobial peptides.

E. Shapiro

Biomolecular computing and its medical applications
E. Shapiro, none

High-throughput Computer-Aided Design, Manufacturing and Application
E. Shapiro, none

Human and mouse cell lineage trees
E. Shapiro, Prof. Nava Dekel, Prof. Karl Skorecki, Dr Liran Shlush

M. Sharon

Studying large protein complexes involved in the protein degradation pathway using a novel mass spectrometry approach.

1.  Elucidating the subunit organization of the 19S complex

2.  Structure-function relationship of the signalosome complex

3.  Investigation of the 20S ubiquitin-independent degradation pathway

Y. Shechter

Mechanism of insulin action: Post-binding events in insulin action

1.  Post-receptor agents mimicking insulin.

2.  Effect of vanadium in vivo and in vitro.

3.  Role of protein tyrosine kinases and protein phosphotyrosine phosphatases in insulin effects.

4.  Inhibitors of tyrosine kinases.

5.  Chemical modifications of peptides and protein drugs.

6.  Novel technologies to prolong life time of peptide and protein drugs.

D. Tawfik

Evolution and mechanism of enzymes

1.  Molecular evolution in man-made cell-like compartments.

2.  Directed evolution of tailor-made hydrolases (esterases, phosphoesterases, organophosphate hydrolases, and amidases) and DNA-modifying enzymes.

3.  Structure, mechanism and evolution of serum paraoxonases (PONs)

4.  The role of promiscuity and conformational plasticity in protein evolution.

5.  Directed evolution of DNA-methyltransferases and DNase inhibitors

6.  The stability effects of mutations

7.  Protein evolvability

8.  Chaperones and protein evolution

M. Walker

Selective gene expression in pancreatic beta cells:

1.  Role of specific transcription factors in expression of the insulin gene in pancreatic beta cells and in control of pancreatic development.

2.  Novel beta cell specific genes: isolation, characterization and use as potential tools in diagnosis and therapy of diabetes.

D. Wallach

Regulation of cell death and tissue damage:

1.  Proteins involved in the signaling for the cell-killing (apoptotic and necrotic), immunoregulatory, and inflammatory functions of cytokines of the tumor necrosis factor (TNF) family, and in the regulation of these functions.

2.  In vivo models for the functions of the signaling mechanisms activated by ligands of the TNF family and for their pathological aberrations.

3.  Natural antagonists to ligands of the TNF family, for protection against the deleterious effects of these cytokines in autoimmune and infectious diseases.

4.  Regulation of the activity of the NF kappa B transcription factors.

5.  The caspases, their functions and mechanisms of activation.

6.  Molecular mechanisms for chronic inflammatory skin diseases.

7.  Contributions of aberrations in the function of signaling proteins activated by ligands of the TNF family to cancer

8.  cancer-cells' survival factors

A. Yaron

Mechanisms of axonal degeneration

Signaling mechanisms of axonal guidance cues