Department of Molecular Genetics 

Adi Kimchi, Head

Research in this department focuses on the utilization of molecular genetics for the study of diverse biological processes, including the study of viruses, control of cell growth and death, cytokines and receptors, human genetic disorders, gene expression, intracellular trafficking and development. Genetic approaches are being used in model organisms and mamalian cell cultures for studying developmental processes and basic cellullar events such as apoptosis. The molecular basis of human genetic diseases is being explored and various mice model systems were generated for this purpose. Another focus of the department is on genomics and computational biology. Utilization of quantitative approaches is undertaken for the analysis of the wealth of information provided by the completed genome sequences and the accumulating gene expression data from DNA arrays.

N. Barkai 

Developing new computation tools for analyzing large-scale gene expression data ("DNA chips").

Quantitative study and modeling of morphogen gradients in Drosophila.

J. Beckmann

Positional cloning of inherited diseases.

Pharmacogenetics.

Modeling the impact of coding SNPs on protein's structures and functions.

A. Elson 

In particular, analysis of the role of protein tyrosine phosphatase Epsilon (PTPe) in mouse physiology and tumorigenesis using molecular, cellular, and whole-animal (transgenic and knockout mice) approaches. Major topics studied include:

1.  The role of PTPe in mammary tumorigenesis/breast cancer.

2.  The role of PTPe in myelination of axons in the nervous system.

3.  The role of PTPe in regulating bone mass.

4.  Identification of substrates and interactors of PTPe.

5.  Characterization of alternative isoforms of PTPe.

6.  Obtaining molecular-level insight into the details and consequences of protein dephosphorylation by PTPe.

Analysis of how physiological processes are regulated by protein dephosphorylation.

J. Gerst 

The Molecular Basis for Secretion and Polarized Cell Growth: SNAREs, SNARE regulators, and Secretory Vesicles

1.  Role of SNAREs (vesicle fusion proteins) and SNARE regulators in exocytosis and endocytosis.

2.  Role of phosphorylation in the control of SNARE assembly and membrane fusion.

3.  Molecular requirments for the biogenesis of secretory vesicles

4.  Mechanisms of mRNA transport in the control of polarized cell growth

Y. Groner 

Positive and negative transcriptional regulation by Runx3

The Human Leukemia Associated Transcription Factor RUNX1/AML1 and Down syndrome leukemia

Biological function of the RUNX transcription factors

Molecular genetics of Down syndrome.

C. Kahana 

Characterization of the regulation and role of polyamines during growth of mammalian cells

1.  Regulation of ornithine decarboxylase expression.

2.  Polyamines and apoptosis.

Identification and characterization of regulatory and structural components of the polyamine transport system.

1.  Characterization of the proteolytic machinery.

2.  Characterization of ornithine decarboxylase sequences that mediate its recognition by the proteolytic machinery.

Identification and characterization of functional domains of mammalian ornithine decarboxylase.

Characterization of ornithine decarboxylase degradation.

A. Kimchi 

Deciphering molecular networks underlying apoptosis and other basic biological processes.

1.  Structure/function studies of DAP genes - a set of pro-apoptotic proteins isolated by a functional approach to gene cloning.

2.  Implication of DAP genes in cancer development and in the control of cellular events such as protein translation initiation, and cytoskeletal organization.

3.  Function-based gene "hunting" and the development of novel strategies to identify the basic principles of complex molecular networks.

D. Lancet 

Genomic and evolutionary analyses of molecular recognition systems.

1.  Identification and molecular cloning of members of the olfactory receptor multigene family, including studies of their genome organization, evolution and polymorphisms in humans.

2.  Computer analyses of structural models of olfactory receptors and other transmembrane proteins and of receptor affinity distributions.

3.  Bioinformatics analysis of long-range DNA sequences and development of whole-genome databases.

4.  Computer simulations of selection and evolution in current living organisms and at the origin of life.

S. Pietrokovski 

Developing computational methods for using and identifying protein motifs and applying them for the analysis of particular protein families.

1.  Developing advanced methods for comparing protein motifs.

2.  Applying protein motif comparisons for functional and structural predictions and to database annotation.

3.  Analysis of inteins ("protein splicing" elements) and homing endonucleases.

Y. Pilpel 

Genome-wide analysis of genetics regulatory networks

Specificity-determining factors in receptor-ligand interactions

O. Reiner 

Formation of the brain structure in human is a complex process. One of the most striking features of the human brain is characteristic convolutions. These convolutions are lacking in a severe human brain malformation known as lissencephaly (smooth brain).

1.  Identification of genes that are downstream to Lis1 mutation using microarray technology.

2.  Study of LIS1 and DCX functions through characterization of protein interactions

3.  Analysis of the developmental function of LIS1, DCX and Doublecortin-like-kinase using gene targeting in the mouse.

Functional Analysis of Genes Involved in Lissencephaly.

M. Revel

Applications of IL-6 Chimera and Interferon-beta in neurology, hematopoiesis, and oncology.
M. Revel, J. Chebath

Interleukin-6 Chimera, a superactivator of the gp130 receptor system: role in nerve myelination, neuroprotection and in the development of neuro-glial cells from embryonic tissues and stem cells.
M. Revel, J. Chebath

Transdifferentiation of neural crest cell derived melanoma into myelinating Schwann cell. Genes controlling cell growth, differentiation, melanogenesis and synthesis of myelin proteins.
M. Revel, J. Chebath

M. Rubinstein 

Physiology and pathology of Interleukin-18 binding protein (IL-18BP), regulation of IL-18BP gene expression, gene therapy with IL-18BP.
M. Rubinstein, D. Novick

Role of leptin in angiogenesis, tumor development and fertility.

L. Sachs 

Stem cell biology: Molecular control of development of normal hematopoietic and leukemic stem cells and apoptosis.
L. Sachs, J. Lotem

1.  Cytokine and apoptosis gene networks in the development of normal and malignant stem cells.

2.  Molecular pathways for apoptosis, differentiation and the suppression of malignancy.

3.  Therapeutic applications of hematopoietic cytokines and stem cell biology.

Y. Shaul 

Study of proteasomal p53 and p73 degradation by a mechanism that does not involve ubiquitination.
Y. Shaul, C. Kahana

The mechanisms of cell response to double-strand DNA break. In particular understanding the roles of p73 and c-Abl.

RFX1 is a unique transcription activator. It teaches us how a single protein acts as both activator and repressor of transcription.

Transcription regulation of the hepatitis B virus. The aim is to understand how overlapping promoters are autonomously functional.

The molecular basis of virus-host cell interaction. How the X protein of HBV modifies cell behavior.

Development of new antiviral strategies that involves gene therapy technologies.

Generation of semi “synthetic viruses”. The aim is to develope the safest macromolecule delivery vehicle.

B. Shilo 

Development of the Drosophila tracheal system.

Signaling by the Drosophila EGF receptor pathway during development.

R. Simantov 

Molecular mechanisms controlling neuronal cell death and drug addiction

1.  Programmed cell death in the brain: Genes activated by neuroactive agents working via neurotransporters.

2.  Involvement of serotonin transporters in neuronal plasticity, growth and neurotoxicity; studies with knockout mice.

3.  Reward and reinforcement mechanisms in the nervous system: Interactions with dopamine, serotonin and glutamate networks.

T. Volk 

The molecular basis for muscle-tendon interactions during embryonic development

1.  The mechanism by which the RNA-binding protein Held out wing regulate tissue differentiation in Drosophila.

2.  The mechansim of muscle attraction by tendon cells.

3.  Structure-function analysis of Kakapo, a cross-linker between the actin and the microtubule networks in tendon cells.

4.  The involvement of Quaking in Schwann cell maturation.