Department of Biological Chemistry

Eitan Reuveny, 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. Several groups investigate the basic principles governing protein-protein interactions; composition, assembly, and architecture of multi-enzyme and other large complexes; catalytic mechanisms and the evolution of proteins and enzymes. A major aim is to understand how the findings relate to intricate biological processes.

  2. DNA and regulation of gene expression. Various aspects of nucleic acids research are addressed in our department including: DNA repair and mutagenesis in mammals; basal and activated transcription; specific gene expression in the pancreas; phylogenetic analysis of accumulated somatic mutations.

  3. Structure, function, and biogenesis of membrane proteins. We investigate important integral membrane proteins on the biochemical, biophysical, structural, and physiological levels. This includes Na+ and K+ channels, Na+/K+ ATPase and its FXYD protein regulators, multidrug transporters, intra-membrane proteases, and peptides that integrate into membranes in various systems.

  4. Membranes, lipids, and organelle structure, function, and biogenesis. Studies in our department include the biosynthetic pathway of membrane proteins; intracellular protein traffic, especially during the process of autophagy; lysosome biogenesis and lipid homeostasis; Calcium homeostasis; and, assembly and function of membrane proteins involved in the immune response, infectious diseases, and viral envelopes.

  5. Signaling within and between cells. Several researchers in the department are interested in problems related to signal transduction. Cell guidance and navigation; axon guidance; cell death and tissue damage; long distance intracellular signaling; regulation of expression of virulence factors; regulation of the circadian rhythm; epigenetic gene silencing; epigenetics and developmental regulation.

  6. Molecular basis of disease. Many research programs in our department involve human disorders, diseases, and syndromes. This includes inflammation, infections and antibiotic resistance, organophosphate detoxification, obesity and diabetes, cancer, and lysosomal storage diseases. Many of these disorders are investigated at the molecular level.


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, 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 of coding and non-coding genes

  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 TISU element

  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 and function of acetylation of the response regulator

  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.


S. Fleishman

Computational design of protein function

  1.  Computational design and experimental characterization via in vitro evolution of high affinity interactions

  2.  The role of multispecificity in small signaling networks

  3.  Specificity and multispecificity in membrane-protein interactions

  4.  Design of membrane-protein interactions


A. Futerman

The molecular mechanisms of sphingolipid storage diseases (Gaucher disease).

The regulation of ceramide synthesis


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.


D. Mirelman

Molecular pathogenesis of the human intestinal parasite Entamoeba histolytica.
D. Mirelman, Rivka Bracha

  1.  Molecular biology and genome organization in the lower eukaryot Entamoeba histolytica.

  2.  Selective inhibition of expression of virulence genes by Antisense RNA.

  3.  Transcriptional epigenetic gene silencing mechanisms

  4.  Pathogenesis of Amoebiasis

  5.  Development of vaccine against Entamoeba histolytica.

Mode of action and therapeutical potential of Allicin from Garlic
D. Mirelman, Aharon Rabinkov, Elena Appel

  1.  Uses of derivatives of Allicin against hypertension and obesity

  2.  Antifungal delivery system which produces in situ toxic allicin molecules

  3.  A delivery system for the in-vivo killing of cancer cells by Allicin


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

High-throughput Computer-Aided Design, Manufacturing and Application

Human and mouse cell lineage trees
E. Shapiro, 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.  Developing novel methodological approaches for structural mass spectrometry

  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


M. Wilchek

Study and application of molecular biorecognition

  1.  Avidin-biotin system: Studies of the strong binding using chemical, physical and biological methods; new applications of the system.

  2.  Affinity chromatography: Studies to improve purification of protein by developing new carriers, new activation methods and new principles.

  3.  Affinity therapy: Development of methods to couple drugs and toxins to biological carriers, such as antibodies, and their delivery to target cells.


A. Yaron

Mechanisms of axonal degeneration

Signaling mechanisms of axonal guidance cues