Department of Molecular Genetics 

Yosef Shaul, Head

The genetic and molecular basis of biological processes is under investigation in this Department. The investigators approach these processes from the most reduced and reconstructed systems up to more systemic and computational analyses. Different organisms are employed including virus, yeast, Drosophila, mouse and human. These animal models and cell culture systems are used to study the mechanisms of;
a. Basic processes in gene expression, such as transcription, translation and protein degradation.
b. Cellular responses to various stimuli, such as cytokines, growth factors and exposure to DNA-damage.
c. Regulation of cell growth and death during development and under other physiological conditions.
d. Development of various organs, such as brain, muscles, bones and pancreas.
e. Genetic and acquired diseases such as cancer.
f. The evolution of genes and their diversifications.

N. Barkai 

Robustness and scaling of morphogen gradients .

System Biology: from functional genomics to network analysis

A. Elson 

Regulation of physiological processes by protein dephosphorylation.

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

2.  The role of tyrosine phosphatases in regulating bone mass and osteoporosis.

3.  Roles of tyrosine phosphatases in regulating body mass.

4.  Characterization of alternative isoforms of PTPe.

5.  Identification of substrates and interactors of PTPe.

J. Gerst 

The Molecular Basis for Polarized Cell Growth: Vesicle and mRNA Transport

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

2.  Phosphorylation in the control of SNARE assembly and membrane fusion.

3.  Molecular requirements for the biogenesis of secretory vesicles

4.  mRNA transport and the control of polarized cell growth in yeast

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.

E. Hornstein 

miRNA role in metazoan development and evolution

1.  miRNA role in craniofacial development

2.  miRNA role in pancreas development

3.  miRNA role in neuronal development

4.  miRNA role in bone and cartilage development

5.  miRNA canalize development

miRNA role in human disease

1.  miRNA role in Diabetes MellitusmiRNA role in neurodegeneration

2.  miRNA role in DiGeorge syndrome

3.  miRNA role in neurodegeneration

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. Rubinstein 

Role of cytokine-induced proteins in atherosclerosis

Cross-talk of transcription factors in interferon-induced genes

Evolution of the interferon alpha gene family

Cytokine receptors and binding proteins
M. Rubinstein, Daniela Novick

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.

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/Shortstop, a cross-linker between the actin and the microtubule networks in tendon cells.

4.  Maturation of Drosophila perineural cells

E. Zelzer

the roles of the VEGF pathway in different steps during skeletal development.

Studying the role of mechanical load on embryonic bone development