Cellular and Developmental Biology

The cell is surrounded by a membrane, which differentiates between it and the extracellular environment. In eukaryote organisms (with a nucleus), the cell can be divided into two major areas: the nucleus and the cytoplasm. The cytoplasm contains all the structures necessary for the cell's existence, which are usually divided into organelles that help in respiration, excretion, metabolism, growth, transport, as well are structures which are important for stabilizing the cell's architecture (the cell skeleton). The nucleus contains the genetic material (DNA) which is packaged in structures called chromosomes. The chromosomes contain genes which produce RNA molecules that are important for producing the cell's proteins. The nucleus also contains one or more nucleoli and is surrounded by the nuclear membrane. The nucleolus is an active site for synthesis of unique RNA and produces most of the cellular RNA required for the cytoplasmatic machines that produce proteins (the ribosomes). The nuclear envelope separates between the genetic material in the nucleus and the cytoplasm where the proteins are produced. The living cell can receive signals from the outside which influence the metabolism in the cell, the growth rate and decisions regarding cell death. These signals are transferred via receptors in the cell membrane and can in the end affect the activity of genes and different activities of cytoplasmatic organelles. Research in the field of cell biology is very broad and in general focuses on understanding the processes that were described above: in molecular terms (research of molecules that participate in the various processes), in structural terms (understanding the production and degradation of structures and molecules), in biochemical terms (research of the biochemical reactions that take place in the various organelles), in kinetic terms (research of the movement of organelles and molecules within the living cell), and in genetic terms (understanding how changes in the genetic charge can lead to changes in the structure or the processes that take place inside the cell, which may help cause different diseases, such as cancer). Developmental biology investigates the wonderful process by which a single cell (the zygote) turns into a complex embryo and an adult. Developmental biology is by nature multidisciplinary and recruits diverse fields of research including genetics, molecular biology, cell biology, computational biology and evolution. The research topics include differentiation mechanisms, morphogenesis and regeneration, sex determination, regulation of gene expression and intercellular communication. Developmental biology has great biotechnological and medical importance, beginning with the identification of the genetic basis of different developmental diseases and the creation of laboratory animal models for human genetic diseases, and ending with tissue cultures and use of embryonic stem cells for research and treatment of different diseases.

Prof. Appelbaum Lior

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    Prof. Breitbart Haim

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      Prof. Cohen Haim

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        Prof. Don Jeremy (Rami)

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          Dr. Hakim Ofir

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            Dr. Hendel Ayal

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              Prof. Juven-Gershon Tamar

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              Publications

              Publications

              1. Even D.Y., Kedmi A., Ideses D. and Juven-Gershon T. (2017) Functional Screening of Core Promoter Activity. Methods Mol Biol. 1651, 77-91

              2. Sameach, H., Narunsky, A., Azoulay-Ginsburg, S., Gevorkyan-Aiapetov, L., Zehavi, Y., Moskovitz, Y., Juven-Gershon, T., Ben-Tal, N. and Ruthstein, S. (2017) Structural and Dynamics Characterization of the MerR Family Metalloregulator CueR in its Repression and Activation States. Structure. 25, 1-9

              3. Chen, D., Orenstein, Y., Golodnitsky, R., Pellach, M., Avrahami, D., Wachtel, C., Ovadia-Shochat, A., Shir-Shapira, H., Kedmi, A., Juven-Gershon, T., Shamir, R., Gerber, D. (2016) SELMAP - SELEX affinity landscape MAPping of transcription factor binding sites using integrated microfluidics. Scientific Reports, 6, 33351

              4. Even, D.Y. *, Kedmi, A. *, Basch-Barzilay, S. *, Ideses, D., Tikotzki, R., Shir-Shapira, H., Shefi, O. and Juven-Gershon, T. (2016) Engineered Promoters for Potent Transient Overexpression. PLoS ONE, 11(2): e0148918

              *The first three authors contributed equally to this paper

              5. Sloutskin, A., Danino, Y.M., Orenstein, Y., Zehavi, Y., Doniger, T., Shamir, R. and Juven-Gershon, T. (2015) ElemeNT: A Computational Tool for Detecting Core Promoter Elements. Transcription, 6(3), 41-50 


              6. Shir-Shapira, H.*, Sharabany,J.*, Filderman, M., Ideses, D., Ovadia-Shochat, A., Mannervik, M. and Juven-Gershon, T. (2015) Structure-Function Analysis of the Drosophila melanogaster Caudal provides insights into core promoter-preferential activation. Journal of Biological Chemistry, 290(28), 17293-305


              *The first two authors contributed equally to this paper

              7. Danino,Y.M, Even, D., Ideses, D.,  and Juven-Gershon,T. (2015) The core promoter: at the heart of gene expression.  BBA Gene Regulatory Mechanisms, 1849(8), 1116-31

              8. Zehavi, Y*., Kedmi, A.*, Ideses, D., and Juven-Gershon, T. (2015) TRF2: TRansForming the view of general transcription factors. Transcription, 6:1, 1-6 


              *The first two authors contributed equally to this paper

              9. Safra, M., Fickentscher, R., Levi-Ferber, M., Danino, Y.M., Haviv-Chesner, A., Hansen, M., Juven-Gershon, T., Weiss, M. and Henis-Korenblit, S. (2014) The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote endoplasmic reticulum homeostasis. Cell Metabolism, 20, 870-881

              10. Kedmi, A.*,  Zehavi, Y*.,  Glick, Y., Orenstein, Y., Ideses, D., Wachtel, C.,  Doniger, T., Waldman Ben-Asher, H., Munster, N., Thompson, J., Anderson, S., Avrahami, D., Yates, JR 3rd, Shamir, R., Gerber, D., and Juven-Gershon, T.   (2014) TRF2 Is a Preferential Core Promoter Regulator. Genes & Development , 28, 2163-2174 


              *The first two authors contributed equally to this paper

              11. Zehavi, Y., Sloutskin, A., Kuznetsov, O., and Juven-Gershon, T. (2014) The core promoter composition establishes a new dimension in developmental gene networks.  Nucleus, 5:4, 298–303

              12. Zehavi, Y., Kuznetsov, O., Ovadia-Shochat, A. and Juven-Gershon, T. (2014) Core promoter functions in the regulation of gene expression of Drosophila Dorsal target genes. Journal of Biological Chemistry, 289, 11993-12004

              
13. Cianfrocco, M.A., Kassavetis, G.A., Grob, P., Fang, J., Juven-Gershon, T., Kadonaga, J.T. and Nogales, E. (2013) Human TFIID binds to core promoter DNA in a reorganized structural state. Cell, 152, 120-131

              14. Juven-Gershon, T. and Kadonaga, J.T. (2010) Regulation of gene expression via the core promoter and the basal transcriptional machinery. Developmental Biology, 339, 225-229

              - One of the top-five most cited articles published in the journal Developmental Biology during the period 1/1/2009-31/12/2011

              15. Juven-Gershon, T., Hsu, J.-Y. and Kadonaga, J.T. (2008) Caudal, a key developmental regulator, is a DPE-specific transcriptional factor. Genes & Development, 22, 2823-2830

              16. Hsu, J.-Y, Juven-Gershon, T., Marr, M.T. 2nd, Wright, K.J., Tjian, R. and Kadonaga, J.T. (2008) TBP, Mot1, and NC2 establish a regulatory circuit that controls DPE-versus TATA-dependent transcription. Genes & Development, 22, 2353-2358

              17. Juven-Gershon, T., Hsu, J.-Y. Theisen J.W.M. and Kadonaga, J.T. (2008) The RNA polymerase II core promoter – the gateway to transcription. Current Opinion in Cell Biology, 20, 253-259

              18. Juven-Gershon, T., Hsu, J.-Y. and Kadonaga, J.T. (2006) Perspectives on the RNA polymerase II core promoter. Biochemical Society Transactions 34, 1051-1054

              19. Juven-Gershon, T., Cheng, S. and Kadonaga, J.T. (2006) Rational design of a super core promoter that enhances gene expression. Nature Methods, 3, 917 - 922

              - Potential applications of this study were discussed in: Perkel, J.M. (2007) Studies you can use. The Scientist, 21,63

              20. Susini, L.*, Passer, B.J.*, Amzallag-Elbaz, N.*, Juven-Gershon, T.*, Prieur, S., Privat, N., Tuynder, M, Gendron M., Israel, A., Amson, R., Oren, M. and Telerman, A. (2001) Siah1 binds and regulates the function of Numb. Proc. Natl. Acad. Sci. USA, 98, 15067-15072

              *The first four authors contributed equally to this paper

              21. Unger, T.*, Juven-Gershon, T.*, Moallem, E.*, Berger, M., Vogt-Sionov, R., Lozano, G., Oren, M. and Haupt, Y. (1999) Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. EMBO J., 18, 1805-1814

              *The first three authors contributed equally to this paper

              22. Elkeles, A., Juven-Gershon, T., Israeli, D., Wilder, S., Zalcenstein, A. and Oren, M. (1999) The c-fos proto-oncogene is a target for transactivation by the p53 tumor suppressor. Molecular and Cellular Biology, 19, 2594-2600

              23. Juven-Gershon, T. and Oren, M. (1999) Mdm2: the ups and the downs. Molecular Medicine, 5, 71-83

              24. Juven-Gershon, T., Shifman, O., Unger, T., Elkeles, A., Haupt, Y. and Oren, M. (1998) The Mdm2 oncoprotein interacts with the cell fate regulator Numb. Molecular and Cellular Biology, 18, 3974-3982

              25. Barak, Y., Gottlieb, E., Juven-Gershon, T. and Oren, M. (1994) Regulation of mdm2 expression by p53: alternative promoters produce transcripts with nonidentical translation potential. Genes & Development, 8, 1739-1749

              26. Barak, Y., Lupo, A., Zauberman, A., Juven, T., Aloni-Grinstein, R., Gottlieb, E., Rotter, V. and Oren, M. (1994) Targets for transcriptional activation by wild-type p53: endogenous retroviral LTR, immunoglobulin-like promoter, and an internal promoter of the mdm2 gene. Cold Spring Harb Symp. Quant. Biol., 59, 225-235

              27. Soussan, L., Tchernakov, K., Bachar-Lavi, O., Juven, T., Wertman, E. and Michaelson, D.M. (1994) Antibodies to different isoforms of the heavy neurofilament protein (NF- H) in normal aging and Alzheimer's disease. Molecular Neurobiology, 9, 83-91

              28. Juven, T., Barak, Y., Zauberman, A., George, D.L. and Oren, M. (1993) Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. Oncogene, 8, 3411-3416

              29. Barak, Y., Juven, T., Haffner, R. and Oren, M. (1993) mdm2 expression is induced by wild type p53 activity. EMBO J., 12, 461-468

              Patents

              1. Optimized core promoters and uses thereof. Kadonaga and Gershon. Patent no. US 7,968,698 B2: 2006.

               

              80-558 Transcriptional Regulation in Eukaryotes

              80-242, 80-220-30 Molecular Biology and Genetic Engineering

              80-937 Biotechnology Seminar for Graduate Students

              80-410 Biotechnology Seminar for third year undergraduate students

              Prof. Korenblit Sivan

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              Publications

              1. Levi-Ferber M, Gian H, Dudkevich R, Henis-Korenblit S (2015) Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans. Elife. doi: 10.7554/eLife.08005.

              2. Levi-Ferber M, Salzberg Y, Safra M, Haviv-Chesner A, Bülow HE, Henis-Korenblit S (2014) It's All in Your Mind: Determining Germ Cell Fate by Neuronal IRE-1 in C. elegans. PLoS Genet. 10(10):e1004747. doi: 10.1371/journal.pgen.1004747.

              3. Safra M, Fickentscher R, Levi-Ferber M, Danino YM, Haviv-Chesner A, Hansen M, Juven-Gershon T, Weiss M and Henis-Korenblit S (2014)The FOXO Transcription Factor DAF-16  Bypasses ire-1 Requirement to Promote Endoplasmic Reticulum Homeostasis.  Cell Metabolism 20(5):870-881.http://dx.doi.org/10.1016/j.cmet.2014.09.006.

              4. Safra M, Henis-Korenblit S (2014) A new tool in C. elegans reveals changes in secretory protein metabolism in ire-1-deficient animals. Worm:e27733. doi: 10.4161/worm.27733.

              5. Safra M, Ben-Hamo S, Kenyon C and Henis-Korenblit S. (2013) The ire-1 ER Stress-Response Pathway is Required for Normal Secretory-Protein Metabolism in C. elegans. J. Cell Sci. 126(Pt 18):4136-46. doi: 10.1242/jcs.123000.

              6. Henis-Korenblit S, Zhang P, Hansen M, McCormick M, Lee SJ, Cary M and Cynthia Kenyon (2010) Insulin/IGF-1 Signaling Mutants Reprogram ER-stress Response Regulators to Promote Longevity. Proc Natl Acad Sci USA.107(21):9730-35.

              7. Ghazi A., Henis-Korenblit S. and Cynthia Kenyon (2009) A transcription elongation factor that links signals from the reproductive system to lifespan extension in Caenorhabditis elegans. PLoS Genet. 5(9):e1000639.

              8. Marash L., Liberman N., Henis-Korenblit S., Sivan G., Reem E., Elroy-Stein O. and Kimchi A. (2008) DAP5 promotes cap-independent translation of Bcl-2 and CDK1 to facilitate cell survival during mitosis. Mol. Cell 30(4):447-59.

              9. Ghazi A.*,Henis-Korenblit S.* and Kenyon C. (2007) Control of C. elegans lifespan by a proteasomal E3-ligase complex. Proc Natl Acad Sci USA. 104(14):5947-52.  *Co-first authorship, these authors contributed equally to the paper.

              10. Henis-Korenblit S., Shani G., Sines T., Marash L., Shohat G. and Kimchi A. (2002) The caspase cleaved DAP5 protein supports internal ribosome entry site mediated translation of death proteins.Proc Natl Acad Sci USA. 99(8):5400-5.

              11. Shani G., Henis-Korenblit S, Jona G., Gileadi O.,Eisenstein M., Kimchi A. (2001). Autophosphorylation restrains the apoptotic activity of DRP-1kinase by controlling dimerization and CaM binding. EMBO J. 20(5):1099-113.

              12. Henis-Korenblit S*, Strumpf NL*, Goldstaub D, Kimchi A (2000). A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation. Mol. Cell Biol. 20(2):496-506.   *Co-first authorship, these authors contributed equally to the paper.

              13. Tzahar E, Pinkas-Kramarski R, Moyer JD, Klapper LN, Alroy I, Levkowitz G, Shelly M, Henis S, Eisenstein M, Ratzkin BJ, Sela M, Andrews GC, Yarden Y (1997). Bivalence of EGF-like ligands drives the ErbB signaling network. EMBO J. 16(16):4938-50.

              14. Andres C, Beeri R, Friedman A, Lev-Lehman E, Henis S, Timberg R, Shani M, Soreq H (1997). Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Ibeta gene expression followed by late-onset neuromotor deterioration. Proc Natl Acad Sci USA. 94(15):8173-8.

              “Basic Cell Biology ” for 1st year undergraduate students

              “Introduction to Biology Laboratory course” for 1st year undergraduate students, 

              “Cellular stress responses” for 3rd year undergraduate and graduate students, 

              Graduate and undergraduate seminar courses, 

              Advanced lab project - Mentoring undergraduate students in a practical lab project

               

              Prof. Malik Zvi

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                Dr. Motro Benny

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                Publications

                He, Y., Zeng, M.Y., Yang, D., Motro, B., and Núñez, G. (2016). NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature 530, 354–357.

                Lachke, S.A., Higgins, A.W., Inagaki, M., Saadi, I., Xi, Q., Long, M., Quade, B.J., Talkowski, M.E., Gusella, J.F., Fujimoto, A., et al. (2012). The cell adhesion gene PVRL3 is associated with congenital ocular defects. Hum. Genet. 131, 235–250.

                Lerer-Goldshtein, T., Bel, S., Shpungin, S., Pery, E., Motro, B., Goldstein, R.S., Bar-Sheshet, S.I., Breitbart, H., and Nir, U. (2010). TMF/ARA160: A key regulator of sperm development. Dev. Biol. 348, 12–21.

                Noy-Lotan, S., Dgany, O., Lahmi, R., Marcoux, N., Krasnov, T., Yissachar, N., Ginsberg, D., Motro, B., Resnitzky, P., Yaniv, I., et al. (2009). Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated. Haematologica 94, 629–637.

                Levitan, D., Lyons, L.C., Perelman, A., Green, C.L., Motro, B., Eskin, A., and Susswein, A.J. (2008). Training with inedible food in Aplysia causes expression of C/EBP in the buccal but not cerebral ganglion. Learn. Mem. 15, 412–416.

                Feige, E., Shalom, O., Tsuriel, S., Yissachar, N., and Motro, B. (2006). Nek1 shares structural and functional similarities with NIMA kinase. Biochim. Biophys. Acta 1763, 272–281.

                Yissachar, N., Salem, H., Tennenbaum, T., and Motro, B. (2006). Nek7 kinase is enriched at the centrosome, and is required for proper spindle assembly and mitotic progression. FEBS Lett. 580, 6489–6495.

                Sredni, B., Gal, R., Cohen, I.J., Dazard, J.-E., Givol, D., Gafter, U., Motro, B., Eliyahu, S., Albeck, M., Lander, H.M., et al. (2004). Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression. FASEB J. 18, 400–402.

                Feige, E., and Motro, B. (2002). The related murine kinases, Nek6 and Nek7, display distinct patterns of expression. Mech. Dev. 110, 219–223.

                Fliess, A., Motro, B., and Unger, R. (2002). Swaps in protein sequences. Proteins 48, 377–387.

                Ben-Zur, T., Feige, E., Motro, B., and Wides, R. (2000). The mammalian Odz gene family: homologs of a Drosophila pair-rule gene with expression implying distinct yet overlapping developmental roles. Dev. Biol. 217, 107–120.

                Kandli, M., Feige, E., Chen, A., Kilfin, G., and Motro, B. (2000). Isolation and characterization of two evolutionarily conserved murine kinases (Nek6 and nek7) related to the fungal mitotic regulator, NIMA. Genomics 68, 187–196.

                Lourenssen, S., Motro, B., Bernstein, A., and Diamond, J. (2000). Defects in sensory nerve numbers and growth in mutant Kit and Steel mice. Neuroreport 11, 1159–1165.

                Chen, A., Yanai, A., Arama, E., Kilfin, G., and Motro, B. (1999). NIMA-related kinases: isolation and characterization of murine nek3 and nek4 cDNAs, and chromosomal localization of nek1, nek2 and nek3. Gene 234, 127–137.

                Mesilaty-Gross, S., Reich, A., Motro, B., and Wides, R. (1999). The Drosophila STAM gene homolog is in a tight gene cluster, and its expression correlates to that of the adjacent gene ial. Gene 231, 173–186.

                Reich, A., Yanai, A., Mesilaty-Gross, S., Chen-Moses, A., Wides, R., and Motro, B. (1999). Cloning, mapping, and expression of ial, a novel Drosophila member of the Ipl1/aurora mitotic control kinase family. DNA Cell Biol. 18, 593–603.

                Arama, E., Yanai, A., Kilfin, G., Bernstein, A., and Motro, B. (1998). Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system. Oncogene 16, 1813–1823.

                Schwartz, Y., Ben-Dor, I., Navon, A., Motro, B., and Nir, U. (1998). Tyrosine phosphorylation of the TATA element modulatory factor by the FER nuclear tyrosine kinases. FEBS Lett. 434, 339–345.

                Klüppel, M., Donoviel, D.B., Brunkow, M.E., Motro, B., and Bernstein, A. (1997). Embryonic and adult expression patterns of the Tec tyrosine kinase gene suggest a role in megakaryocytopoiesis, blood vessel development, and melanogenesis. Cell Growth Differ. 8, 1249–1256.

                Yanai, A., Arama, E., Kilfin, G., and Motro, B. (1997). ayk1, a novel mammalian gene related to Drosophila aurora centrosome separation kinase, is specifically expressed during meiosis. Oncogene 14, 2943–2950.

                Mélet, F., Motro, B., Rossi, D.J., Zhang, L., and Bernstein, A. (1996). Generation of a novel Fli-1 protein by gene targeting leads to a defect in thymus development and a delay in Friend virus-induced erythroleukemia. Mol. Cell. Biol. 16, 2708–2718.

                Motro, B., Wojtowicz, J.M., Bernstein, A., and van der Kooy, D. (1996). Steel mutant mice are deficient in hippocampal learning but not long-term potentiation. Proc. Natl. Acad. Sci. U. S. A. 93, 1808–1813.

                Fode, C., Motro, B., Yousefi, S., Heffernan, M., and Dennis, J.W. (1994). Sak, a murine protein-serine/threonine kinase that is related to the Drosophila polo kinase and involved in cell proliferation. Proc. Natl. Acad. Sci. U. S. A. 91, 6388–6392.

                Motro, B., and Bernstein, A. (1993). Dynamic changes in ovarian c-kit and Steel expression during the estrous reproductive cycle. Dev. Dyn. 197, 69–79.

                Letwin, K., Mizzen, L., Motro, B., Ben-David, Y., Bernstein, A., and Pawson, T. (1992). A mammalian dual specificity protein kinase, Nek1, is related to the NIMA cell cycle regulator and highly expressed in meiotic germ cells. EMBO J. 11, 3521–3531.

                Motro, B., van der Kooy, D., Rossant, J., Reith, A., and Bernstein, A. (1991). Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci. Development 113, 1207–1221.

                Motro, B., Itin, A., Sachs, L., and Keshet, E. (1990). Pattern of interleukin 6 gene expression in vivo suggests a role for this cytokine in angiogenesis. Proc. Natl. Acad. Sci. U. S. A. 87, 3092–3096.

                Prof. Shav-Tal Yaron

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