Research at the NIBN Engineering affinity scaffolds for cancer imaging and therapy Itay Cohen and Dr. Niv Papo Research at the NIBN Ben-Gurion UNIVERSITY OF THE NEGEV Contents NIBN Overview 5 Cancer Research Group 6 Dr. Eyal Arbely 7 Dr. Roi Gazit 8 Dr. Dan Levy 9 Dr. Niv Papo 10 Prof. Angel Porgador 11 Dr. Barak Rotblat 12 Prof. Varda Shoshan-Barmatz 13 Autoimmune and Metabolic Diseases Group 14 Prof. Amir Aharoni 15 Prof. Angel Porgador 16 Prof. Assaf Rudich 17 Prof. Orian Shirihai 18 Neurodegenerative Diseases Group 19 Dr. Anat Ben-Zvi 20 Prof. Alon Monsonego 21 Prof. Israel Sekler 22 Prof. Varda Shoshan-Barmatz 23 Infectious Diseases Group 24 Dr. Natalie Elia 25 Dr. Eyal Gur 26 Dr. Tomer Hertz 27 Prof. Michael M. Meijler 28 Human Genetic Disorders Group 29 Prof. Ohad Birk 30 Prof. Ruti Parvari 31 Dr. Esti Yeger-Lotem 32 Applied Biotechnology Group 33 Prof. Ohad Medalia 34 Prof. Amir Sagi 35 Dr. Raz Zarivach 36 Dr. Stas Engel 37 Infra-Structure Supporting Group 38 Bioinformatics Core Facility 39 Crystallography Unit 40 Genetics Unit 41 Cytometry, Proteomic and Microscopy Unit 42 Dr. Roee Atlas 43 NIBN Overview The National Institute for Biotechnology in the Negev Using these approaches, NIBN has already succeeded (NIBN) Ltd. is the first, self-organized, independent to generate commercial outlets in the fields of drug scientific research and development (R&D) body in targets for cancer therapy and infectious diseases, Israel. It has been established through a tri-lateral anti-inflammatory drugs as well as major advances agreement between the government of Israel, in aquaculture technology. These initial commercial Ben-Gurion University of the Negev (BGU) and successes have all been guided by NIBN’s highly philanthropist, Dr. Edgar de Picciotto. In November experienced management team. 2009, the NIBN became a company and implemented a detailed, 8 year applicable-orientated R&D program In December 2014, NIBN members located in several to specifically allow scientific excellence with a BGU buildings will relocate to The Edgar de Picciotto commercial outlet, funded by the NIBN. Family National Institute for Biotechnology in the Negev, a new 5400 sq m building. The building has The missions of the NIBN are to bridge the gap been carefully designed to provide state-of-the- between basic and applied research as well as art scientific infra-structure and to accelerate the forming a major channel between applied science institute’s development and growth, as well as to and industry, resulting in the establishment of a host start-up companies, with the aim of leveraging scientific infrastructure for biotechnology industry in additional commercial activities. the Negev. The strengths of the NIBN are derived from a combination of outstanding scientists, conducting NIBN’s ultimate goals are primarily driven by two multi-disciplinary research with both basic and issues. Firstly, the recruitment of outstanding biotechnological implications, close cooperation scientists as reflected in their academic excellence, with BGU departments, faculties, and research achievements and biotechnological implications of centers, all under the umbrella of a state-of-the-art, their research. Secondly, NIBN’s revered international scientific infrastructure. Such features coalesce to Scientific Advisory Board (SAB) composed of Nobel permit scientific excellence and create the required Prize laureate Prof. Sir Aaron Klug, FRS as well as leverage for the emergence of an internationally- distinguished scientists Prof. Raymond Dwek, FRS, acclaimed and successful biotechnology institute in Prof. Philip Needleman, Prof. Richard Ulevitch, Prof. the Negev and in Israel. Nathan Nelson and Prof. Hermona Soreq. The SAB sets a gold standard of scientific excellence, long- In order to fulfill this ultimate goal, the NIBN term scientific goals and major guidance concerning strongly encourages and funds “cutting-edge”, commercial efforts. creative research in the fields of Cancer Research, Infectious Diseases, Human Genetic Disorders, This booklet presents the current members of the Neurodegenerative Diseases, Autoimmune and NIBN, their selected research projects as well as the Metabolic Diseases and Applied Biotechnology. The Institute's core service facilities. It is our hope that resultant “value through innovation” fuels a plethora the information in this booklet will serve as a major of new biotechnology applications and commercial stepping stone in solidifying the NIBN as a World-Class opportunities. Such business development outlets Research Institute in biotechnology and fostering include: a) the creation of “spin-out” companies commercial opportunities with industry. David Ben- through funding bodies; b) joint collaborative efforts Gurion wrote that “the ultimate test for Israel in our with Big Pharma’; c) exclusive out-licensing of a generation is to prevail, through the power of science technology or product to biotechnology companies. and a pioneering spirit over the wide expanses of the south and the Negev”. At the NIBN, we are translating this vision into reality. 5 Cancer Research Group An estimated 14 million cancer cases occurred world-wide during 2012 which is expected to increase to about 24 million by 2035. While having a wide diversity of cancer types and characterizations, all cancer types involve several hallmarks include sustaining proliferative signaling, evading growth suppressors and resisting cell death. NIBN’s cancer research group focuses on multi-disciplinary themes including understanding cancer biology through epigenetic modifications (eg. DNA and protein methylation changes), metabolic re-programing, the role of dysregulated cell growth, evading apoptotic cell death and mitochondrial involvement (via voltage-dependent anion channels), the development of appropriate immune-stimulatory strategies by targeting Proliferating Cell Nuclear Antigen (PCNA), the development of innovative animal models to simulate human leukemias and solid cancers, development of innovative diagnostic tools and the rationale design of small molecules, siRNA’s, peptides and protein-based anti-cancer therapeutics including bispecific molecules. • Dr. Eyal Arbely • Dr. Roi Gazit • Dr. Dan Levy • Dr. Niv Papo • Prof. Angel Porgador • Dr. Barak Rotblat • Prof. Varda Shoshan-Barmatz 6 Expanding the repertoire of ribosomally-synthesized proteins Dr. Eyal Arbely Background The translation mechanism has been evolved over hundreds of millions of years to translate 64 triple-nucleotide codons, each encoding either one of the common 20 amino acids, or the termination of translation. Yet, this machinery is far from exploiting its full potential – proteins with expanded chemistry can be ribosomally synthesized by site-specific incorporation of non-proteinogenic amino acids, using the amber stop codon (UAG) and an orthogonal aminoacyl-tRNA synthetase/tRNA pair. The chemical and structural diversity of such proteins can be expanded even further by exploiting the unique chemistry of bacteriocins - ribosomally synthesized peptides, transformed into biologically active compounds by a series of unique structural and chemical post-translational modifications. Our laboratory is interested in developing and applying different methods for ribosomal expression of chemically and structurally-modified proteins for basic biochemical or biophysical research and as a platform for developing peptide-based, bioactive molecules in Ph.D.: The Hebrew University of general and particularly for novel antibiotics. Jerusalem, Israel Post-doctorate: MRC Center for Current research Protein Engineering and Laboratory of 1. Developing and applying methods for in-vivo Molecular Biology, Cambridge, UK incorporation of non-proteinogenic amino acids: Genetic code engineering allows the site-specific incorporation of Position: Senior Lecturer tailor-made amino acids into recombinant proteins. Equipped with a unique biophysical or chemical property, such amino Department of Chemistry acids may aid in studying the structure and cellular function Faculty of Natural Sciences of proteins. For example, the incorporation of modified amino acids carrying a naturally occurring post-translational E-mail: [email protected] modification such as acetylation or phosphorylation. Using genetic code engineering and directed evolution, we aim Selected publications to develop and apply novel methods for in vivo and in vitro studies of post-translationally modified proteins. Specifically, Arbely E. and Arkin I.T. (2004). Experimental Measurement we are interested in studying the effect of acetylation on the of The Strength of a Cα- H…O Bond in a Lipid Bilayer. J. Am. structure, subcellular localization and DNA binding affinity of Chem. Soc. 126:5362-5363. transcription factors such as NF-κB and p53. In recent years Arkin I.T., Xu H., Jensen M.O., Arbely E., Bennett E.R., Bowers K.J., a direct link was found between acetylation and cellular Chow E., Dror R.O., Eastwood M.P., Flitman-Tene R., Gregersen metabolism. In light of the high frequency of metabolic B.A., Klepeis J.L., Kolossváry I., Shan Y. and Shaw D.E. (2007). disorders associated with diseases ranging from cancer to Mechanism of Na+/H+ Antiporting. Science 317:799-803. obesity, we aim at understanding how cellular metabolism and acetylation level are correlated with acetylation and Arbely E., Rutherford J.T., Sharpe D.T., Ferguson N. and Fersht transcription activity of key transcription factors. A.R. (2009). Downhill versus Barrier-Limited Folding of BBL 1: 2. Bacteriocin