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
naama.barkai@weizmann.ac.il

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

Quantitative study and modeling of morphogen gradients in Drosophila.

J. Beckmann
j.beckmann@weizmann.ac.il

Positional cloning of inherited diseases.

Pharmacogenetics.

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

A. Elson 
ari.elson@weizmann.ac.il

Analysis of how physiological processes are regulated by protein dephosphorylation.

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

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

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

3.  Identification of substrates and interactors of PTPε.

4.  Characterization of alternative isoforms of PTPε.

5.  Obtaining molecular-level insight into the details and consequences of protein dephosphorylation by PTPε.

J. Gerst 
jeffrey.gerst@weizmann.ac.il

The Molecular Basis for Cellular Secretion: 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 SNARE assembly and membrane fusion.

3.  Biogenesis of secretory vesicles and the mechanism of their docking and fusion.

4.  Role of mRNA localization in control of polarized growth in yeast.

Y. Groner
yoram.groner@weizmann.ac.il

Molecular genetics of Down syndrome.

Transgenic and Knock-out mice models for gene dosage effect of Down Syndrome.

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

The Runx3 transcription factor and somatosensory-related ataxia

C. Kahana
chaim.kahana@weizmann.ac.il

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
adi.kimchi@weizmann.ac.il

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 
doron.lancet@weizmann.ac.il

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
shmuel.pietrokovski@weizmann.ac.il

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.

O. Reiner 
orly.reiner@weizmann.ac.il

Functional Analysis of Genes Involved in Lissencephaly.

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 function through characterization of protein-protein interactions, and overexpression in tissue culture.

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

M. Revel
michel.revel@weizmann.ac.il

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 
menachem.rubinstein@weizmann.ac.il

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 
leo.sachs@weizmann.ac.il

Stem cell biology: Molecular control 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 hematopoietic stem cells.

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

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

B. Shilo
benny.shilo@weizmann.ac.il

Development of the Drosophila tracheal system.

Signaling by the Drosophila EGF receptor pathway during development.

R. Simantov
rabi.simantov@weizmann.ac.il

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
lgvolk@weizmann.ac.il

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.