Biological Chemistry
Eitan Bibi, Head
The Ruth and Jerome A. Siegel and Freda and Edward M. Siegel Professorial ChairThe Department of Biological Chemistry is home to more than 24 research groups, whose scientific activities span several areas in the Life Sciences. The common thread is the study of the biochemistry of life. Emphasis is on the investigation of proteins, whether soluble or membrane-bound, and their key biological functions. We seek a molecular understanding of their structure, function, and interaction with other factors. A variety of biochemical, biophysical, structural, computational and molecular biological methods are being employed, with many overlapping interests and inter-group collaborations. Current research activities evolve around the following seven foci of interest:
- Protein structure, function, design and evolution
Gideon Schreiber and his coworkers study the basic physico-chemical principles governing protein-protein interactions, and how these relate to complex biological processes. The gained understanding is implemented in several medically relevant systems such as the binding of interferon to its receptor, as well as in algorithm development. Meir Wilchek and his group are studying the structure of avidin and its exceptionally high affinity to biotin. The avidin-biotin complex is being utilized for a variety of new biotechnological applications. Edward A. Bayer and his colleagues are studying the structure, architecture and biotechnological applications of the multi-enzyme cellulosome complex, its interactions with cellulose and other plant cell-wall polysaccharides, and the utilization of recombinant designer cellulosomes for enhanced decomposition of cellulosic substrates in the conversion of biomass to bioenergy. The group of Dan S. Tawfik is interested in the mechanism and evolution of proteins, and enzymes in particular. They perform laboratory evolution experiments aimed at understanding how new proteins evolve, and at the creation of novel enzymes with tailor-made activities. Michal Sharon's goal is to understand the relationship between structure and function of molecular machines involved in the ubiquitin-proteasome pathway. Specifically her group investigates the mechanisms that control and regulate these cellular machines and identifies the network of intermolecular interactions that ensure the integration of this cellular process. A novel mass spectrometry method is utilized for analysis of these multiprotein complexes in their native state. This approach is particularly adept at providing new insights into subunit stoichiometry, composition and structural arrangement.
- Structure and function of ion channels, pumps, other transporters, membrane protein involved in viral infection and innate immunity, viral envelope proteins, and photosynthesis proteins
Several groups are investigating proteins that form specific pores across the cell membrane. Eitan Reuveny is investigating the molecular properties and physiological function of a group of neuronal K+ channels and their interaction with G-proteins. Yechiel Shai's group uses a multidisciplinary approach to study the insertion, assembly and function of membrane proteins involved in immune response (TCR, TLR), infectious diseases (host-defense peptides; i.e. antimicrobial and anticancer peptides), and viral envelopes (HIV/SIV gp41). These studies also led to the design of novel potential antimicrobial, anticancer, immunosuppressive, and antiviral drugs. Nuclear pore complexes, multi-protein structures, that transport macromolecules in and out of the nucleus, are being studied by Ziv Reich. His work utilizes biophysical methods such as atomic force microscopy. Haim Garty focuses on two themes in the regulation of ion transport, which participate in maintaining body salt and water balance. One is the epithelial Na+ channel, which mediates the aldosterone-dependent Na+ reabsorption in the kidney and intestine, and the other is a new group of tissue specific regulators of the Na+/K+ ATPase, the FXYD proteins. Steven J. D. Karlish and his colleagues are exploring the structure and organization of Na,K-ATPase, and its regulation by FXYD proteins. This ion pump plays a central role in maintaining Na and K gradients across the cell membrane and is involved in the pathophysiology of essential hypertension. Another family of transport proteins, which extrude toxins from cells and hence pose a major obstacle in cancer chemotherapy and antibiotic treatment, is being studied by Eitan Bibi. The groups of Steven J. D. Karlish and Eitan Bibi are also interested in solving membrane protein structures by X-ray crystallography. Other researchers are interested in photosynthesis and its relation to ion transport. Shmuel Malkin's research in photosynthesis concentrated on interpreting photoacoustic signals from plant leaves under special conditions, which indicate gas uptake. These signals may be related to oxygen photoreduction by photosystem I and/or proton movements to the thylakoid lumen. Uri Pick's group studies the mechanism by which the alga Dunaliella copes with extreme salinity and iron deprivation and also collaborates with Avihai Danon (Plant Sciences) to develop technologies to produce biodiesel from green algae. The groups of Uri Pick and Ada Zamir are collaborating to elucidate the mechanisms by which the green alga Dunaliella copes with extreme changes in external salinity and with iron deprivation.
- Mechanisms by which proteins and lipids are transported from their point of synthesis, sorted, and inserted into various organelles
Studies related to this general problem in cell biology are being carried out in a number of laboratories. Eitan Bibi and his co-workers are studying the role of the signal recognition particle (SRP) and other cellular components in the biogenesis of prokaryotic membrane proteins. They seek to identify new components of the machinery, and to understanding how ribosomes target and associate with the membrane, and how membrane protein synthesis is regulated. Zvulun Elazar is investigating intracellular protein traffic in eukaryotic systems. His work has led to the identification of new factors that couple transport vesicles to cytoskeletal elements. Delivery of lipids to the cell membrane, and their role in neuronal growth is being studied by Tony Futerman works on two main areas, namely the lysosomal storage diseases, Gaucher, Tay-Sachs, and Niemann-Pick disease; recently, together with I. Silman and J. Sussman he solved the structure of Cerezyme, the enzyme given to Gaucher disease patients. The other area concerns mechanisms of ceramide signaling, and has characterized a gene family encoding mammalian ceramide synthases.
- Signal transduction, and molecular pathogenesis
Several researchers in the department are interested in problems related to signal transduction, chemotaxis and pathogenesis. Michael Eisenbach’s group is investigating, at the molecular level, how bacteria navigate according to chemical cues (chemotaxis), and how human sperm cells are guided to the egg. In bacteria, they focus on the mechanism by which the switch of the flagellar motor receives signals from the receptors and modulates the direction of flagellar rotation. In sperm, the Eisenbach group showed that guidance is essential for fertilization and it involves at least two mechanisms: chemotaxis and thermotaxis. The group of David Wallach is studying mechanisms that control cell death and tissue damage, and involve the caspase cysteine-protease family, and transcription factors of the NF-kB family. They have cloned and characterized several proteins that participate in the induction of cell death and inflammation by receptors of the TNF/NGF family, and explore their mechanisms of action. Using transgenic mouse models, they currently focus on elucidating the contribution of genetic variations in these proteins to skin pathology, inflammatory disorders and cancer. Retrograde signaling complexes which govern neuronal growth and regeneration are being investigated by Michael Fainzilber and his co-workers. They have identified new targeting and scaffolding proteins that enable axon-cell body communication in neurons. David Mirelman and his co-workers are characterizing regulatory mechanisms that control the expression of virulence factors in the human intestinal protozoan parasite, /Entamoeba histolytica/ and in particular, epigenetic gene silencing mechanisms. Other studies, in collaboration with the group of Meir Wilchek, focus on the therapeutic properties of the biologically active garlic molecule Allicin and the development of in-situ, targeted delivery systems. Yoram Shechter's research activities focus on overcoming states of insulin-resistance, prolonging the actions of peptide/protein drugs in vivo and delivering peptides and protein drugs from the periphery to the brain via the blood brain barrier. Ruth Miskin is utilizing transgenic mice that over-express plasminogen activator in order to understand mechanisms whereby caloric restriction attenuates aging and increases life-span. Therapeutic and pathogenic signals of the cell membrane, in tumor cells that are subjected to hydrostatic pressure are being examined by Meir Shinitzky. In addition, he investigates the effect on differentiation in breast cancer cells and neuoronal cells of cyclic phosphates, signaling molecules that originate from phospholipid degradation. Ehud Shapiro' s group is using a high-level computer process description language, Stochastic Pi Calculis, to mathematically specify and simulate signal transduction pathways.
- Genome maintenance and function: DNA repair and gene expression
Zvi Livneh and his coworkers are exploring the molecular mechanisms of DNA repair and mutagenesis in mammals, and in particular translesion DNA synthesis (TLS) by specialized DNA polymerases, and the role of DNA repair in cancer susceptibility. Recently they discovered that TLS is regulated by p53 via p21 to maintain a low mutation load. They also discovered that reduced activity of the DNA repair enzyme OGG1 is a risk factor in lung and head and neck cancers. Two groups are studying mechanisms mediating regulation of gene expression. Rivka Dikstein and her associates are studying the mechanisms of basal and activated transcription. Specifically they are investigating the general transcription factor TFIID at the biochemical and molecular level, the mammalian core promoter, links between transcription and post transcriptional stages of gene expression and the mechanism underlying rapid transcription activation by NF-kappaB. Michael Walker and colleagues are investigating the regulation of specific gene expression in insulin-producing pancreatic beta cells, and how embryonic stem cells can be induced to develop efficiently into beta cells. Recent studies have revealed that activity of GPR40, a novel beta cell receptor, helps explain the important, yet poorly understood connection between obesity and diabetes.
- Mechanisms of developmental regulation
Avraham Yaron’s group is studying the molecular mechanisms that govern axon guidance during embryonic development. They focus on the mechanisms by which guidance receptors are regulated, and how these receptors transmit their signals. Yoav Soen's group is using embryonic stem cells models to study how different layers of regulation interact to specify morphogenetic decisions, how these decisions are shaped by interactions between emerging precursors and how they are coordinated across a developing embryonic tissue.
- Biolmolecular computers and computation-based cell lineage analysis
Ehud Shapiro and his team are investigating the engineering of computers made of biological molecules. They succeeded to construct a finite automaton made of DNA and enzymes, which is capable of sensing and diagnosing molecular disease symptoms, and in response releasing a drug-like molecule in a test-tube model system. In a different direction, advanced computational techniques combined with somatic mutation analysis are used for reconstructing cell lineage trees in cultured cells and in mice.http://www.weizmann.ac.il/Biological_Chemistry/
Research Staff, Visitors and Students
Professors
Ed Bayer, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Maynard I. and Elaine Wishner Professorial Chair of Bio-Organic Chemistry
Eitan Bibi, Ph.D., Hadassah Medical School, The Hebrew University of Jerusalem, Jerusalem, Israel
The Ruth and Jerome A. Siegel and Freda and Edward M. Siegel Professorial Chair
Michael Eisenbach, Ph.D., Tel Aviv University, Tel-Aviv, Israel
The Jack and Simon Djanogly Professorial Chair of Biochemistry
Anthony H. Futerman, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Joseph Meyerhoff Professorial Chair of Biochemistry
Haim Garty, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Hella and Derrick Kleeman Professorial Chair of Biochemistry
Steven J.D Karlish, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The William D. Smithburg Professorial Chair of Biochemistry
Zvi Livneh, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Maxwell Ellis Professorial Chair of Biomedical Research
Yechiel Shai, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Harold S. and Harriet B. Brady Professorial Chair of Cancer Rrsearch
Yoram Shechter, Ph.D., Weizmann Institute of Science, Rehovot, Israel (on extension of service)
The Charles H. Hollenberg Professorial Chair of Diabetes and Metabolic Research
David Wallach, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
The Joseph and Bessie Feinberg Professorial Chair
Professors Emeriti
S. Roy Caplan, Ph.D., University of Witwatersrand, Johannesburg, South Africa
David Danon, Ph.D., University of Geneva, Geneva, Switzerland
Carlos Gitler, Ph.D., University of Wisconsin, Madison, United States
Ora Kedem, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Shmuel Malkin, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Israel R. Miller, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
David Mirelman, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Nathan Sharon, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Meir Wilchek, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Ada Zamir, Ph.D., Technion-Israel Institute of Technology, Haifa, Israel
Associate Professors
Rivka Dikstein, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Ruth and Leonard Simon Professorial Chair of Cancer Research
Zvulun Elazar, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Harold L. Korda Professorial Chair of Biology
Michael Fainzilber, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
The Chaya Professorial Chair in Molecular Neuroscience
Uri Pick, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Charles and Louise Gartner Professorial Chair
Ziv Reich, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Eitan Reuveny, Ph.D., Northwestern University Medical School, Chicago, United States
Gideon Schreiber, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Dan Tawfik, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Nella and Leon Benoziyo Professorial Chair
Michael Walker, Ph.D., Weizmann Institute of Science, Rehovot, Israel
The Marvin Myer and Jenny Cyker Professorial Chair of Diabetes Research
Senior Scientists
Michal Sharon, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Incumbent of the Elaine Blond Career Development Chair
Yoav Soen, Ph.D., Technion - Israel Institute of Technology, Haifa, Israel
Incumbent of the Daniel E. Koshland Sr. Career Development Chair
Avraham Yaron, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Senior Staff Scientists
Rivka Adar, Ph.D., Tel Aviv University, Tel-Aviv, Israel
Carol Asher, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Daniel M. Tal, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Associate Staff Scientists
Elena Bochkareva, Ph.D., Institute of Protein Research, Academy of the USSR, Pushchino, Russian Federation
Ruti Kapon, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Adriana Katz, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Tamar Paz-Elizur, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Assistant Staff Scientists
Gili Ben-Nissan, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Yael Fridmann Sirkis, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Moshe Goldsmith, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Daniel Harari, Ph.D., University of Melbourne, Melbourne, Australia
Andrew Kovalenko, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Yael Pewzner-Jung, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Senior Interns
Anat Bahat, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Konstantin Bogdanov, Ph.D., Tel Aviv University, Tel-Aviv, Israel
Yael Leitner Dagan, Ph.D., The Hebrew University of Jerusalem, Jerusalem, Israel
Gregory Linshiz, Ph.D., Weizmann Institute of Science, Rehovot, Israel (left March 2010)
Izhak Michaelevski, Ph.D., Tel Aviv University, Rehovot, Israel
Reinat Nevo, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Ida Rishal, Ph.D., Tel Aviv University, Tel-Aviv, Israel
Ziv Sevilya, Ph.D., Tel Aviv University, Tel-Aviv, Israel
Interns
Michael Anbar, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Noam Diamant, Ph.D., Weizmann Institute of Science, Rehovot, Israel
Lior Izhar, Ph.D., Weizmann Institute of Science, Rehovot, Israel (left March 2010)
Consultants
Diana Bach
Rina Barak
Igor Berezovsky, University of Bergen, Norway
S. Roy Caplan
Liat Sara Haklai-Topper (left October 2010)
Na'Aman Kam (left December 2010)
Alon Karpol, Desiger Energy, Science Park, Rehovot, Israel
Uriel Katz, Maccabi, Tel-Hashomer, Israel
Talia Miron
Ruth Miskin
Ely Morag, Designer Energy, Rehovot
Vladimir Potapov (left July 2010)
Yosef Scolnik
Nathan Sharon
Meir Shinitzky
Visiting Scientists
Haim Aakab
Liana Casquinhadasilv, University of Lisbonne, Portugal
Jian Fang Du, University of Beijing, China (P.R)
Mikael Elias
Marc Fellous, INSERM E0021, Paris, France
James Fraser, University of Berkeley, U.S.A.
Wilma Friedman, Rutgers University , NJ, U.S.A.
Erich Gulbins, University of Essen, Germany
Tae-Bong Kang, Technion, Haifa, Israel
Laurence Kedes, University of Southern California, LA, U.S.A.
Acwis Kelly, Weizmann Institute of Science, Israel
Kayzad Nilgiriwala
Sergio Peisajovich
Akhil Rajput
Nadav Sahar, Sheba Medical Ctr., Tel Hashomer, Israel
Merijn Salverda, Wageningen University of Agriculture, Nederland
Kim Soo-Hyun, KonKuk University, Korea
Postdoctoral Fellows
Michael Anbar, Ph.D., Weizmann Institute of Science, Israel
Christopher John Arnusch, Utrecht University
Liat Bahari, Weizmann Institute of Science, Israel
Talya Belogus, Weizmann Institute of Science, Israel
Tuval Ben Yehezkel, Weizmann Institute of Science, Israel
Kfir Ben-Harush, Ben-Gurion University, Israel
Keren Ben-Yaakov, Weizmann Institute of Science, Israel
Konstantin Bogdanov, Tel-Aviv University, Israel
Silvia Chuartzman, Ph.D., Weizmann Institute of Science, Israel
Mati Cohen, Weizmann Institute of Science, Israel
Bareket Dassa, Weizmann Institute of Science, Israel
Noam Diamant, Weizmann Institute of Science, Israel
Jianfang Du, Ph.D., Beijing Institute of Basic Medical Sciences
Rofa Elfakess, Weizmann Institute of Science, Israel
Mikael Hocine Elias, Aix-Marseille Universite
Nir Etkovitz, Bar-Ilan University, Israel
Milana Fraiberg, Tel-Aviv University, Israel
Kfir Gazit, Weizmann Institute of Science, Israel
Binyamin Gil, Weizmann Institute of Science, Israel
Saar Golan, Ph.D., Technion - Israel Institute of Technology, Israel
Michal Golan-Mashiach, Weizmann Institute of Science, Israel
Ronit Gutman-Pasvolsky, Weizmann Institute of Science, Israel
Liraz Harel, Weizmann Institute of Science, Israel
Haim Haviv, Weizmann Institute of Science, Israel
Ayal Hendel, Weizmann Institute of Science, Israel
Adrian Hugenmatter, Swiss Federal Institute of Technology (Ethz)
Yuval Inbar, Tel-Aviv University, Israel
Daniel Kaganovich, Ph.D., Stanford University
Na'Aman Kam, Ph.D., Weizmann Institute of Science, Israel
Einat Kapri-Pardes, Ph.D., Agriculture Faculty, Israel
Olga Khersonsky, Weizmann Institute of Science, Israel
Jin-Chul Kim, Weizmann Institute of Science, Israel
Yakov Kipnis, Ph.D., Weizmann Institute of Science, Israel
Chunjin Li, Jilin University
Irina Lubarski, Weizmann Institute of Science, Israel
Neeraj Kumar Mishra, Ph.D., Jawaharlal Nehru University, New Delhi
Ilit Noach, Ph.D., Weizmann Institute of Science, Israel
Marc Nathan Offman, Ph.D., University College London
Raz Palty, Ben-Gurion University, Israel
Joo-Won Park, Ewha Womans University
Marek Rajman, Ph.D., Institute of Animal Biochemistry And Genetics Sasc
Akhil Rajput, Ph.D., Weizmann Institute of Science, Israel
Viji Raveendran Nair Indi, University of Kerala
Adi Raveh, Weizmann Institute of Science, Israel
Avi Raveh, Tel-Aviv University, Israel
Peter Reuven, Weizmann Institute of Science, Israel
Gabriela Ridner, Weizmann Institute of Science, Israel
Liat Shimon, Ph.D., Weizmann Institute of Science, Israel
Elena Shvets, Weizmann Institute of Science, Israel
Misha Soskine, Ph.D., Hebrew University of Jerusalem, Israel
Petro Starokadomskyy, Ph.D., Institute of Molecular Biology & Genetics Nasu
Beata Toth-Cohen, University of Debrecen
Tapesh Kumar Tyagi, V.P.Chest Institute, University of Delhi , Delhi-0
Shelly Tzlil, Hebrew University of Jerusalem, Israel
Sameer Kumar Vidhya Bahuleyan, University of Kerala
Hilla Weidberg, Weizmann Institute of Science, Israel
Itamar Yadid, Weizmann Institute of Science, Israel
Ganit Yarden, Weizmann Institute of Science, Israel
Research Students
Adi Abada Manelis Livnat Afriat-Gorno Orly Ester Alber Muhammad Ali Amir Apelbaum Leah Armon Avraham Ashkenazi Omri Avidan Tali Avnit-Sagi Muneef Ayyash Keren Bahar Halpern Hagit Bar Nadav Bar Sagi Barzilai Roy Bekerman Rotem Ben Tov Perry Tuval Ben Yehezkel Oshrit Ben-David Daniel Ben-Halevy Keren Ben-Yaakov Adi Bercovich Kinori Marina Cherniavsky-Lev Ori Cohavi Isadora Cohen Mati Cohen Tomer Cohen Ayelet Cooper Shachar Dagan Shlomi Dagan Lital Davidi Eynat Dellus Alik Demishtein Gil Diamant Elizabeta Dinitz Michael Elgart Shirley Elias Racheli Erez-Roman Eli Ezrielev Tamar Farfel Becker Avner Fink Nir Fluman Erez Shaul Garty Kfir Gazit Amir Gelman Binyamin Gil Michal Golan-Mashiach Liora Guy David Liraz Harel Michal Harel Haim Haviv Ayal Hendel Maya Kahan Haggai Kaspi Elad Lavee Laviad Doron Levin Elena Levin Carni Lipson Elinor Malul-Erez Adva Mansura Maya Maor Yonit Marcus-Perlman Adi Minis Guy Mlechkovich Natali Molotski Oren Moscovitz Shiri Moshitzky Ekaterina Petrovich Yael Phillip Tatyana Rachutin - Zalogin Adi Raveh Eliran-Moshe Reuven Peter Reuven Liat Rockah- Shmuel Erez Romi Shelly Rozen Meir Rozenbaum Zohar Schoenmann Sigal Shachar Revital Sharivkin Tomer Shpilka Tal Shprung Hadar Sinvani Michal Slutzki Shay Stern Rotem Tidhar Osnat Tirosh Agnes Toth-Petroczy Onie Tsabari Yael Vazana Anna Veprik Einat Vitner Hilla Weidberg Alon Wellner Seung-Hoon Yang Eliyahu Yosef Ido Yosef Dmitry Yudin Gabriel Zarbiv Lior Zelcbuch Omer Ziv Administrator
Maanit Zibziner