Uri Gophna
e-mail: urigo@tauex.tau.ac.il
Member of the Edmond J. Safra Center for Bioinformatics
Research Interests
Microbial Evolution. Understanding evolutionary processes behind bacterial adaptation has contributed to both the medical community and to evolutionary theory. Broadly, our research interests revolve around two related topics: 1. The role of lateral gene transfer (LGT) in the evolution of microorganisms and 2. The study of host-microbe interactions, with particular focus on interactions between bacterial pathogens and multi-cellular eukaryotic hosts that result in disease. We are interested in fundamental questions in microbial ecology and evolution: How does host specificity evolve? How did virulence factors originate, and did they descend from proteins that ancestrally mediated interactions with unicellular eukaryotes, or are they instead products of gene recruitment from unrelated bacterial functions? Which forces shape the population structure of microbial communities in the mammalian microbiota?
Microbial ecology in health and disease. The mammalian intestinal microbiota (also known as gut flora) is a complex ecosystem containing hundreds of microbial species, with and bacterial cells in our body vastly outnumber our own cells. The microbiota not only contributes to the nutrition and gut development of the host but is also required for development of a healthy immune response, and is, to some degree, genetically determined. The human microbiota has been attracting tremendous interest and has been mentioned as one of the "Areas to Watch for 2008” in Science's Breakthrough of the Year. Recently, there is increasing evidence supporting the involvement of the gut microbiota in several human diseases such as inflammatory bowel diseases, colorectal cancer and irritable bowel syndrome as well as disease-promoting conditions such as obesity. However, due to its amazing complexity and the limitation of current microbe cultivation techniques, the microbiota remains a poorly understood ecosystem, in need of further research. We study the human microbiota using metagenomic techniques, and analyze samples from both healthy individuals and patients with Crohn's disease, irritable bowel syndrome and colorectal cancer, to try and explore the different roles the microbiota plays in these diseases.
Impact of lateral gene transfer on microbial evolution. LGT plays a crucial role in the evolution of microorganisms, including pathogens, and is a major source of genetic innovation. Many known virulence factors are the product of LGT, probably because the strong selective advantage they confer greatly increases the genes' chances of being fixed in a population. Using a variety of bioinformatic approaches we identify new laterally transferred genes and study their evolution. We also investigate why some gene functions are transferred frequently while others are only rarely horizontally acquired. We are particularly interested in cases where such genes are the driving forces behind bacterial speciation and virulence. We are also interested in inter-species recombination, a process which was believed to be extremely rare but, is now known to exist in several prokaryotic groups.
A link to our publications in Pub Med
A link to our publications in Pub Med
My "official" webpage in Tel-Aviv University:
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PhD Students:
Itay Amir
e-mail: mailto:itayamir@gmail.com
Research Interests
I am working on a very interesting ecological ecosystem: the gut microbiota. This amazing field has been revisited in the past decade using molecular ecological techniques based on the 16S ribosomal RNA gene sequences and metagenomics.
I am interested in the interaction between the host and the microbiota in states of disturbance, such as a disease. I am using a murine model of colorectal cancer to follow changes in the fecal microbiota and am conducting a study of comparing intestinal biopsy samples from colorectal cancer patients and healthy individuals.
Publications
Publications
Yosepha Yeshaya, Itay Amir, Ayelet Rimon, Jane Freedman, Mordechai Shohat, Lydia Avivi (2009) .Microdeletion syndromes disclose replication timing alterations of genes unrelated to the missing DNA .Molecular Cytogenetics 2:11.http://www.molecularcytogenetics.org/content/2/1/11
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Nirit Keren-Weinberg
e-mail: kerennir@post.tau.ac.il
Research interests
Bile acids and the gut microbiota have an important role in digestion and healthy gut function. In my studies I investigate the interaction between bile acids and the intestinal microbiota, and their possible role in functional gastrointestinal disorders. I do this by analyzing samples from people before and after they undergo gall-bladder removal (cholecystectomy), and comparing microbial community and bile acid profiles. Cholcystectomy changes the way in which bile acids are secreted to the bile and the amount of bile acids that is secreted after every meal. This is probably why many people report changes in bowel habits after this operation. Furthermore, about 10% of people after cholecystectomy suffer from diarrhea. I hope that understanding the interactions between the gut microbiota and bile acids will improve our understanding of healthy gut function as well as help prevent post- cholecystectomy diarrhea.
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The capacity of bacteria and other microbes to exchange genes through LGT is an important phenomenon with implications for ecology, evolution, biotechnology and medicine, and is a major force in microbial evolution, driving bacterial genetic innovation and speciation.
Though LGT has been most extensively described between bacteria, there is still much room for research concerning interactions between hosts and microbes of different domains of life. The aim of my work is to explore the extent and variety of such LGT events between hosts and microbes, and to assess its effect on their interactions. Such events includes inter-domain transfers spanning across all three domains of life: Archea, Bacteria and Eukarya.
1. Alon Wellner, Mor Lurie and Uri Gophna (2007) “Complexity, connectivity, and duplicability as barriers to lateral gene transfer”, Genome Biology, 8: R156.
2. Mor N. Lurie-Weinberger, Laura Gomez-Valero, Nathalie Merault, Gernot Glöckner, Carmen Buchrieser and Uri Gophna. "The origins of eukaryotic-like proteins in Legionella pneumophila" Int. J. Med. Microbiol. (2010), doi:10.1016/j.ijmm.2010.04.016.
3. Mor N Lurie-Weinberger; Michael Peeri, Uri Gophna. Contribution of lateral gene transfer to the gene repertoire of a gut-adapted methanogen. Genomics (2011).
4. Avital Brodt, Mor N Lurie-Weinberger and Uri GophnaCRISPR Loci Reveal Networks of Gene Exchange in Archaea.
5. Mor N Lurie-Weinberger; Michael Peeri, Uri Gophna. Extensive inter-domain lateral gene transfer in the evolution of the human commensal Methanosphaera stadtmanae. Front Genet. 2012;3:182. doi: 10.3389/fgene.2012.00182. Epub 2012 Sep 19.
6. Pasternak Z, Pietrokovski S, Rotem O, Gophna U, Lurie-Weinberger MN, Jurkevitch E. By their genes ye shall know them: genomic signatures of predatory bacteria. ISME J. 2012 Nov 29. doi: 10.1038/ismej.2012.149. [Epub ahead of print]
3. Mor N Lurie-Weinberger; Michael Peeri, Uri Gophna. Contribution of lateral gene transfer to the gene repertoire of a gut-adapted methanogen. Genomics (2011).
4. Avital Brodt, Mor N Lurie-Weinberger and Uri GophnaCRISPR Loci Reveal Networks of Gene Exchange in Archaea.
5. Mor N Lurie-Weinberger; Michael Peeri, Uri Gophna. Extensive inter-domain lateral gene transfer in the evolution of the human commensal Methanosphaera stadtmanae. Front Genet. 2012;3:182. doi: 10.3389/fgene.2012.00182. Epub 2012 Sep 19.
6. Pasternak Z, Pietrokovski S, Rotem O, Gophna U, Lurie-Weinberger MN, Jurkevitch E. By their genes ye shall know them: genomic signatures of predatory bacteria. ISME J. 2012 Nov 29. doi: 10.1038/ismej.2012.149. [Epub ahead of print]
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I am working on the very interesting third domain of life –the Archaea. Focusing on the halophilic archaon Haloferax volcanii I ask two different questions:
What are the barriers for inter-species recombination in Archaea, via natural mating. We test this by mating the two closely related halophilic Archaea, Haloferax volcanii and Haloferax mediterranei and testing recombination frequencies.
What is the role of the highly conserved KEOPS complex in Archaea. The KEOPS complex is composed of several key proteins, the main of which is the Kae1. Homologs of Kae1, also called O-sialoglycoprotease (OSGEP) or GCP (glycopeptidase), are encoded in every sequenced genome in the three domains of life.
Publications:
1. Naor A, Lazary R, Barzel A, Papke R. T and Gophna U. (2011). In vivo characterization of the homing endonuclease within the polB gene in the halophilic archaeon Haloferax volcanii. PLoS One. Jan 20;6(1):e15833.
2. Barzel A, Naor A, Privman E, Kupiec M and Gophna U. (2011). Homing endonucleases residing within inteins: evolutionary puzzles awaiting genetic solutions. Biochem Soc Trans. Jan 19;39(1):169-73.
3. Barzel A, Privman E, Peeri M, Naor A, Shachar E, Burstein D, Lazary R, Gophna U, Pupko T, Kupiec M.(2011) Native homing endonucleases can target conserved genes in humans and in animal models. Nucleic Acids Research. Aug;39(15):6646-59.
4. Naor A, Mevarech M, Lapierre P, Papke R. T and Gophna U. Low Species Barriers in Halophilic Archaea and the Formation of a Recombinant Hybrid, Current Biology (2012), doi:10.1016/j.cub.2012.05.056
Highlighted in: Nature Reviews Microbiology 10, 522-523 (August 2012) " Archaea: Breaking down the species barrier
Dispatch: Current Biology, 22 Issue 15, 7 (August 2012): Prokaryotic Sex: Eukaryote-like Qualities of Recombination in an Archaean Lineage: Frederick M. Cohan and Stephanie Aracena
Dispatch: Current Biology, 22 Issue 15, 7 (August 2012): Prokaryotic Sex: Eukaryote-like Qualities of Recombination in an Archaean Lineage: Frederick M. Cohan and Stephanie Aracena
5. Naor A, Thiaville P. C, Altman-Price N, Cohen-Or I, Allers T, de Crécy-Lagard V and Gophna U. Genetic investigation of the KEOPS complex in halophilic archaea. PLoS ONE 2012;7(8)e43013.
6. Naor A, Gophna U. Cell fusion and hybrids in Archaea - prospects for genome shuffling and accelerated strain development for biotechnology. Bioengineered, In Press.
6. Naor A, Gophna U. Cell fusion and hybrids in Archaea - prospects for genome shuffling and accelerated strain development for biotechnology. Bioengineered, In Press.
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Gidi G. Pelchovich
e-mail: gidi78@gmail.com
Research Interests
Lateral gene transfer (LGT) is a powerful force in microbial evolution. However, the barriers that restrict this evolutionary phenomenon are not fully understood. When considering transfer events of pre-existing functions, some genes have a higher chance of being fixed in a microbial population than others. According to "Grantham's Genome Hypothesis", genomes of different organisms use different codons more frequently than others to encode a specific amino acid. It therefore follows that in most cases, foreign genes will have dissimilar codon bias from that of the recipient genome, at the time of transfer. In my research, I am investigating the impact of codon usage on lateral gene transfer in microbial community by using genetics and bioinformatics approaches.
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M.Sc students
Adi Ulman
Research Interests:
Candida albicans is the most common fungal human pathogen, although it is also carried by many asymptomatic individuals as a commensal of the gut microbiota. In my research, I try to understand the effects of specific antibiotics, targeted against bacteria, on the emergence of Candida strains that are resistant to antifungal drugs.
e-mail: avitalbr@post.tau.ac.il
Research Interests:
Publications:
Brodt Avital, Lurie-Weinberger Mor.N. and Gophna Uri (2011) CRISPR Loci Reveal Networks of Gene Exchange in Archaea. Biology Direct. 6(1):65.
Avital Brodt
e-mail: avitalbr@post.tau.ac.il
Research Interests:
Crohn's disease, ulcerative colitis and pouchitis are chronic inflammatory bowel diseases (IBDs). The pathogenesis of IBD is still unclear and the condition remains incurable. IBD is associated with a combination of genetic and environmental factors, for example intestinal microorganisms.
With bioinformatics techniques, I am developing a comprehensive computational approach. The goal is to identify and predict the progression of inflammation from different components: genetic susceptibility, expression changes and intestinal microbiota .Publications:
Brodt Avital, Lurie-Weinberger Mor.N. and Gophna Uri (2011) CRISPR Loci Reveal Networks of Gene Exchange in Archaea. Biology Direct. 6(1):65.
Israela Uurgeman
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Research Assistants:
Rachel Schreiber e-mail: schreibe@post.tau.ac.il
Research interests:I am interested in the role of the highly conserved KEOPS complex in Archaea. The KEOPS complex is composed of several key proteins, the main of which is the Kae1. The Kae1 homolog, also called O-sialoglycoprotease (OSGEP) or GCP (glycopeptidase).
I am also interested in the microbiota of patients with Inflammatory Bowel Diseases (IBD) - Crohn's Disease (CD), Ulcerative Colitis (UC), and pouchitis
Publications:
1. Aharonowitz, Y., Av-Gay,Y., Schreiber R., Cohen G., (1993)Characterization of a thioredoxin-like disulfide reductase from Streptomyces clavuligerus and its possible role in b-lactam antibiotic biosynthesis. J.Bacteriol. 175: 623-629
2. Cohen, G., Janko, M., Mislovati,R., Argaman, A., Schreiber, R., Av-Gay, Y., and Aharonowitz, Y., (1993) Thioredoxin-thioredoxin reductase system of Streptomyces clavuligerus: sequence, expression and organization of the genes. J.Bacteriol. 175:5159-5167
3. Cohen,G., Argaman, A., Schreiber, R., Mislovati, M., and Aharonowitz, Y., (1994) The thioredoxin system of Penicillium chrysogenum and its possible role in penicillin biosynthesis. J. Bacteriol. 176: 973-984
4. Masalha, M., Borovok, I., Schreiber, R., Aharonowitz Y., and Cohen., G., (2001) Analysis of Transcription of the Staphylococcus aureus Aerobic Class Ib and Anaerobic Class III Ribonucleotide Reductase Genes in Response to Oxygen. J Bacteriol. 183: 7260-7272
5. Ilya Borovok , Rachel Kreisberg-Zakarin1, Michaela Yanko, Rachel Schreiber, Margarita Myslovati, Fredrik Aslund, Arne Holmgren, Gerald Cohen and Yair Aharonowitz (2002) Streptomyces contain class Ia and class II ribonucleotide reductases expression analysis of the genes in vegetative growth. Microbiology. 148: 391-404
6. Uziel Orit, Ilya Borovok, Rachel Schreiber, Gerald Cohen and Yair Aharonowitz. (2004) Transcriptional regulation of the Staphylococcus aureus thioredoxin and thioredoxin reductase genes in responde to oxygenand disulfide stress. Journal of Bacteriology 186: 326-334
7. Borovok, I., Gorovitz, B., Yanku, M., Schreiber, R., Gust, B., Chater, K., Aharonowitz, Y., Cohen, G., (2004) Alternative oxygen-dependent and oxygen-independent ribonucleotide reductases in Streptomyces: cross-regulation and physiological role in response to oxygen limitation. Molecular Microbiology 54:1022-1035.
8. Borovok, I., Gorovitz, B., Schreiber, R., Aharonowitz, Y., Cohen, G., (2006) Coenzyme B12 Controls Transcription of the Streptomyces Class Ia Ribonucleotide Reductase nrdABS Operon via a Riboswitch Mechanism. J. Bacteriol. 188: 2512-2520.
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Past Members:
Amitai Or
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Amitai Or
e-mail: Amitaior@gmail.com
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