Building: Arthur and Rochelle Belfer Building for Biomedical Research

Tel: 972-8-934-6058

Fax: 972-8-934-4108

e-mail: pilpel@weizmann.ac.il

My Lab Page

A central challenge faced by living cells is to allow for precise gene expression regulatory programs to take place in spite of environmental variations, genetic changes and stochasticity of the internal cellular environment. Gene expression is regulated by control of transcription, RNA degradation, translational and protein degradation. Our lab, by applying genome wide computational approaches, backed-up by in house laboratory experiments, devotes itself to both establishing an in-depth understanding of the different processes controlling gene expression, and to understand how these processes are orchestrated to establish robustness of the regulatory code. To this end, we established dictionaries of the cis-regulatory sequences motifs controlling the initiation of transcription and, thus mRNA synthesis in several organisms. In complement, we perform micro-array experiments combined with computational analysis to determine how mRNA life times are encoded by the 3'-UTR sequence elements associated with their genes. We are also concerned with control of translation by both antisense RNAs and translation efficiency reflected by the adaptation of protein coding sequences and the tRNA repertoire of the organism. In this avenue, we further investigate how different extent of codon adaptations of the same genes in different organisms may derive phenotypic differences between these organisms. To provide robust fulfillment of regulatory gene expression programs cells rely on special genetic circuits that allow them to respond more efficiently to their environment, and to control the internal stochastic fluctuations. We study how these goals are fulfilled by regulating genomic redundancies that offer genetic backup against external and internal variability. We also explore how the regulatory system probabilistically predicts environmental changes before they actually occur. Last, we study how stochasticity within the cell affects expression and regulatory circuits that allow for control of this stochasticity.

Recent References

Man O & Pilpel Y. Phenotypic divergence of yeast species is associated with differential translational efficiency of entire genetic modules. (revised and resubmitted to Nature Genetics).

Lapidot M & Pilpel Y Genome wide overview of natural antisense transcription – how is it regulated, how does it regulate. EMBO report (in press).

Furman I & Pilpel Y Promoting mining of human promoters. News & Views in Molecular Systems Biology.2:2006.0030 (2006)

Kafri R, Levi M & Pilpel Y The regulatory utilization of genetic redundancy through responsive backup circuits. Proc Natl Acad Sci U S A 103(31):11653-8 (2006).

Xi Y, Shalgi R, Fodstad O, Pilpel Y, & Jingfang Ju Differentially regulated miRNAs and actively translated mRNA transcripts by tumor suppressor p53 in colon cancer. Clinical Cancer Research 12(1):2014-24 (2006)

Bar-Even, A, Paulsson J, Pilpel Y* & Barkai N*. Noise in protein expression scales with natural protein abundance. Nature Genetics 36(6) 36-43(2006) *corresponding authors

Nadejda S., Vardy E., Molshanski-Mor S., Eitan A., Pilpel Y, Schuldiner S., & Bibi E. 3D model of the Escherichia coli multidrug transporter MdfA reveals an essential membrane-embedded positive charge. Biochemistry 44(45), 14870-80 (2005).

Shalgi, R. Lapidot, M Shamir, R. & Pilpel Y. A catalog of stability-associated sequence elements in 3’ UTRs of yeast mRNAs. Genome Biology ;6(10):R86. (2005).

Tabach, Y. Milyavsky, M., Zuk O., Yitzhaki A., Shats, I., Domany, E., Rotter, R. & Pilpel, Y. Genome-wide transcription regulatory circuits controlling cellular malignant transformation. Molecular Systems Biology 1:2005.002 (2005)

Kafri, R., Bar-Even, A. & Pilpel, Y. Transcription control reprogramming in genetic backup circuits. Nature Genetics 37(3) 295-9 (2005)

Garten Y*, Kaplan S*, & Pilpel Y. Extraction of Transcription Regulatory Signals from Genome-wide DNA-protein interaction Data. Nucleic Acids Research 33(2) 605-15 (2005) *these authors have equal contribution to the work

Lapidot, M. & Pilpel Y. Comprehensive quantitative analyses of the effects of promoter sequence elements on mRNA transcription. Nucleic Acid Research 31, 3824-8 (2003).

Sudarsanam P., Pilpel, Y., Chrch, G. Genome-wide co-occurrence of promoter elements reveals a cis-regulatory cassette of r-RNA transcription motifs in S. Cerevisiae. Genome Research 12, 1723-1731 (2002) PDF Version

Zhu, Z., Pilpel, Y. and Church., G. Computational identification of transcription factor binding sites via a transcription-factor-cantric clustering (TFCC) algorithm. J. Mol. Biol. 318, 71-81 (2002) PDF Version

Cohen, B., Pilpel, Y., Mitra, R. and Church., G. Discrimination between the Yapp and Yap2p transcription networks on yeast. Mol. Biol. Cell. 13, 1608-1614 (2002) PDF Version

Pilpel, Y., Sudarsanam P. and Church., G. Identifying regulatory networks by combinatorial analysis of promoter elements. Nature Genetics, 29, 153-159 (2001) PDF Version

Fuchs, T., Glusman, G., Horn-Saban, S., Lancet, D. and Pilpel, Y. The human olfactory subgenome: from sequence to structure and evolution. Hum Genet, 108, 1-13 (2001) PDF Version

Lapidot, M., Pilpel, Y., Gilad, Y., Falcovitz, A., Sharon, D., Haaf, T. and Lancet, D. Mouse- human orthology relationships in an olfactory receptor gene cluster. Genomics, 71, 296-306 (2001) PDF Version

Conticello, S.G., Pilpel, Y., Glusman, G. and Fainzilber, M. Position-specific codon conservation in hypervariable gene families. Trends. Genet, 16, 57-59 (2000) PDF Version

Glusman, G., Bahar, A., Sharon, D., Pilpel, Y., White, J. and Lancet, D. The Olfactory receptor gene superfamily: data mining, classification, and nomnclature. Mamm Genome, 11, 1016-1023 (2000) PDF Version

Pilpel, Y., Ben-Tal., N. and Lancet, D. kPROT; a knowledge-based scale for the propensity of residue orientation in trasmembrane segments. Application to membrane protein structure prediction. J Mol Bio, 294, 921-935 (1999) PDF Version

Sharon, D., Glusman, G., Pilpel, Y., Khen, M., Gruetzner, F., Haaf, T. and Lancet, D. Primate Evolution of an olfactory receptor cluster: diversification by gene conversion and recent emergence of pseudogenes. Gemoncs, 61, 24-36 (1999) PDF Version

Pilpel, Y. and Lancet, D. The variable and conserved interfaces of modeled olfactory receptor proteins. Protein Sci, 8, 969-977 (1999) PDF Version

Segre, D., Lancet, D., Kedem, O. and Pilpel, Y. Graded autocatalysis replication domain (GARD): kinetic analysis of self-replication in mutually catalytic sets. Orig Life Evol Biosph, 28, 501-514 (1998) PDF Version

Segre, D., Pilpel, Y. and Lancet, D. Mutual catalysis in sets of prebiotic organic molecules: Evolution through computer simulated chemical kinetics. Physica, 249, 558-564 (1998) PDF Version

Lancet, D., Kedem, O. and Pilpel, Y. Emergence of order in small autocatalytic sets maintained far from equilibrium: application of probabilistic receptor affinity distribution (RAD) model. Ber Bunsgenes Phys Chem, 98, 1166-1169 (1994)

Refereed conference proceedings

Lapidot M & Pilpel Y Characterization of the Effects of TF Binding Site Variations on Gene Expression. Towards Predicting the Functional Outcomes of Regulatory SNPs.
Lecture Notes in Bioinformatics (presented in RECOMB Regulatory Genomics 2005)

Kafri R & Pilpel Y Evidence for evolutionary selection of paralogous functional redundancies. Lecture Notes in Bioinformatics (presented in RECOMB Regulatory Genomics 2005)

Man O Sussman JL & Pilpel Y Examination of the tRNA Adaptation Index as a Predictor of Protein Expression Levels. Lecture Notes in Bioinformatics (presented in RECOMB Regulatory Genomics 2005)