Department of Molecular Genetics
Yosef Shaul, Head
The molecular basis of genetics and related biological processes are 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, senescence, differentiation and death.
d. Development; Mechanistic view of zygote to embryo transition and development of various organs, such as brain, muscles, bones and pancreas.
e. Genetic and acquired diseases such as cancer and virus infection.
f. Computational and system biology. The function/evolution of genes and their diversification.
Genetic regulation of apoptosis and its molecular mechanisms.
Roles of caspases in “conventional” apoptosis and during cellular remodeling.
Robustness and scaling of morphogen gradients .
System Biology: from functional genomics to network analysis
Regulation of physiological processes by protein dephosphorylation.
- The role of PTPe in mammary tumorigenesis/breast cancer.
- The role of tyrosine phosphatases in regulating bone mass and osteoporosis.
- Roles of tyrosine phosphatases in regulating body mass.
- Characterization of alternative isoforms of PTPe.
- Identification of substrates and interactors of PTPe.
Intracellular protein and mRNA transport in cell growth and disease
- SNAREs and SNARE regulators in intracellular protein sorting
- A yeast model for Batten disease
- Targeted mRNA transport and the control of polarized cell growth
- Genome-wide mapping of mRNA localization
- Targeted mRNA transport and organelle biogenesis
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.
miRNA role in metazoan development and human disease
- miRNA role in neuronal development
- miRNA role in pancreas development
- miRNA role in bone and cartilage development
- miRNA stem cell differentiation
miRNA role in human disease
- miRNA role in Diabetes Mellitus
- miRNA role in neurodegeneration
- miRNA role in DiGeorge syndrome
- miRNA role in Tracheomalacia
Characterization of the regulation and role of polyamines during growth of mammalian cells
- Regulation of ornithine decarboxylase expression.
- Polyamines and apoptosis.
Identification and characterization of regulatory and structural components of the polyamine transport system.
- Characterization of the proteolytic machinery.
- 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.
Programmed Cell Death: from single genes and molecular pathways towards systems level studies
- Deciphering the roles of the DAP genes in programmed cell death
- Systems biology analysis of the programmed cell death network
- Functional annotations of a family of death-associated kinases: DAPk, DRP-1 and ZIPk
- Protein translation control during cell death: structure/function analysis of the DAP5 gene
Genomic and evolutionary analyses of molecular recognition systems.
- Identification and molecular cloning of members of the olfactory receptor multigene family, including studies of their genome organization, evolution and polymorphisms in humans.
- Computer analyses of structural models of olfactory receptors and other transmembrane proteins and of receptor affinity distributions.
- Bioinformatics analysis of long-range DNA sequences and development of whole-genome databases.
- Computer simulations of selection and evolution in current living organisms and at the origin of life.
Developing computational methods for using and identifying protein motifs and applying them for the analysis of particular protein families.
- Developing advanced methods for comparing protein motifs.
- Applying protein motif comparisons for functional and structural predictions and to database annotation.
- Analysis of inteins ("protein splicing" elements) and homing endonucleases.
Systems biology of genetics regulatory networks
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).
- Identification of genes that are downstream to Lis1 mutation using microarray technology.
- Study of LIS1 and DCX functions through characterization of protein interactions
- 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.
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 NovickUnderstanding the Molecular Mechanisms Driving Endoplasmic Reticulum Inheritance
Deciphering the Regulatory Mechanisms Driving Insertion and Maturation of Tail Anchored Proteins
M. Schuldiner, Prof. Blanche SchwappachStudy of proteasomal p53 and p73 degradation by a mechanism that does not involve ubiquitination.
The activation and the role of c-Abl-p73 signaling axis in response to DNA damage and cancer.
modulation of Hippo signaling by c-Abl; the role of Yap1 and TAZ transcription coactivators in cell proliferation and in apoptosis
the mechanisms of switching from tumor suppressor to oncogene.
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 HBV modifies cell behavior.
20S proteasome and degradation of unstructured proteines by default; the role of NQO1.
Development of the Drosophila tracheal system.
Signaling by the Drosophila EGF receptor pathway during development.
Computational discovery of novel natural antibiotics
Microbial genomics and RNAomics with Illumina sequencing
CRISPR, an antiviral microbial defense system
The molecular basis for muscle-tendon interactions during embryonic development
- The mechanism by which the RNA-binding protein Held Out Wing (HOW) regulates tissue differentiation in Drosophila.
- The mechansim of muscle attraction by tendon cells.
- The mechanism of arrest of muscle migration.
- Mechanisms regulating heart somatic and visceral muscle morphogenesis
The formation of the Blood Brain Barrier in Drosophila
- 1. The contribution of HOW to BBB formation
- 2. Control of the unique cytoskeletal organization during BBB formation by Moody
- 3. Identification of additional components required for BBB formation.
the roles of the VEGF pathway in different steps during skeletal development.
Studying the role of mechanical load on embryonic bone development