Ehud Shapiro, Ph.D. - Account Profile
As an active scientist for over three decades, I always explored uncharted territories across discipline boundaries, often ahead of my time and often with a long term impact that became apparent only a decade or two later.
Back to 1994. After more than a decade of research at Weizmann on the use of Concurrent Prolog for programming parallel and distributed computers, I felt that our technology is ripe for field testing. I took leave of absence from my position at Weizmann and founded Ubique Ltd., one of the first Internet software companies worldwide. After selling Ubique to America Online in 1995, and deliberating whether to remain in the booming Internet industry or to return to academia, I decided to venture into a self-study of molecular biology. In doing so I was struck by the similarity between molecular machines for DNA replication, transcription and translation and the Turing machine, which since its conception in 1936 is at the foundation of theoretical computer science. Soon after returning to Weizmann in 1998, I presented the vision of "Doctor in a Cell" – a computer made of biological molecules and can operate within a living environment, sensing disease symptoms, analysing them utilizing pre-programmed medical knowledge, and releasing a drug molecule if a disease is diagnosed. This wild vision advanced to become a reality much faster than anyone had anticipated. We presented in Nature in 2001 a programmable, autonomous automaton made of biological molecules, and in Nature in 2004 we showed how can it be extended with an input module that senses molecular markers of cancer and with an output module that can release an anti-cancer drug molecule, and be programmed to release the drug molecule only upon identifying a molecular signature characteristic of cancer, in vitro. On the basis of this work I was awarded an ERC Advanced Grant, was selected as a member of the 2004 “Scientific American 50” and as their Research Leader in Nanotechnology, and received the 2004 Individual Prize in Biotechnology by the World Technology Network.
Work continues vigorously in our lab to advance the vision of biomolecular computing as a basis for future programmable drugs, but we are not alone: The field is now wide open, with many excellent groups joining the fray, and this vision seems now closer than ever to being realized, e.g. a recent Science publication led by Benenson shows a programmable molecular device that can distinguish between cancer and non-cancer cells ex vivo.
Our work at the interface of computer science and molecular biology led to two other interdisciplinary research projects. One project, led in my lab by Dr. Tuval Ben Yehezkel since 2006, aims to develop computer-aided design, manufacturing and applications of DNA libraries. It is the basis of a FET-Open consortium which we lead, called CADMAD. The second project, the cell lineage analysis project, represents the preliminary studies that form the basis of the current research proposal, and is based on a simple idea: Our cell lineage tree is implicitly encoded by the somatic mutations that endow each cell in our body with an almost unique genomic signature. The lineage tree can be reconstructed based on the distances between cellular genomic signatures, if only we can know them.
DNA computing, cell lineage tree, cell lineage analysis, stem cells dynamics,
|22383887||Reizel Y, Itzkovitz S, Adar R, Elbaz J, Jinich A, Chapal-Ilani N, Maruvka YE, Nevo N, Marx Z, Horovitz I, Wasserstrom A, Mayo A, Shur I, Benayahu D, Skorecki K, Segal E, Dekel N, Shapiro E Cell lineage analysis of the Mammalian female germline. (2012) PLoS Genet 8: e1002477 (Added 2012-03-11 10:08:50.7755)|
|22022423||Segev E, Shefer G, Adar R, Chapal-Ilani N, Itzkovitz S, Horovitz I, Reizel Y, Benayahu D, Shapiro E Muscle-bound primordial stem cells give rise to myofiber-associated myogenic and non-myogenic progenitors. (2011) PLoS One 6: e25605 (Added 2012-03-11 10:09:11.768418)|
|21829376||Reizel Y, Chapal-Ilani N, Adar R, Itzkovitz S, Elbaz J, Maruvka YE, Segev E, Shlush LI, Dekel N, Shapiro E Colon stem cell and crypt dynamics exposed by cell lineage reconstruction. (2011) PLoS Genet 7: e1002192 (Added 2012-03-11 10:09:19.044615)|
|21601680||Yehezkel TB, Linshiz G, Kaplan S, Gronau I, Ravid S, Adar R, Shapiro E Recursive construction and error correction of DNA molecules and libraries from synthetic and natural DNA. (2011) Methods Enzymol 498: 207-45 (Added 2012-03-11 10:16:12.266244)|
|21486254||Ben Yehezkel T, Nagar S, Mackrants D, Marx Z, Linshiz G, Shabi U, Shapiro E Computer-aided high-throughput cloning of bacteria in liquid medium. (2011) Biotechniques 50: 124-7 (Added 2012-03-11 10:16:15.172236)|
|21189843||Shabi U, Kaplan S, Linshiz G, Benyehezkel T, Buaron H, Mazor Y, Shapiro E Processing DNA molecules as text. (2010) Syst Synth Biol 4: 227-36 (Added 2012-03-11 10:16:16.905726)|
|19809454||Ran T, Kaplan S, Shapiro E Molecular implementation of simple logic programs. (2009) Nat Nanotechnol 4: 642-8 (Added 2012-03-11 10:11:53.551009)|
|18927381||Shapiro E, Gil B Cell biology. RNA computing in a living cell. (2008) Science 322: 387-8 (Added 2012-03-11 10:11:59.288083)|
|18711638||Baruch L, Itzkovitz S, Golan-Mashiach M, Shapiro E, Segal E Using expression profiles of Caenorhabditis elegans neurons to identify genes that mediate synaptic connectivity. (2008) PLoS Comput Biol 4: e1000120 (Added 2012-03-11 10:12:05.212242)|
|18667587||Ben Yehezkel T, Linshiz G, Buaron H, Kaplan S, Shabi U, Shapiro E De novo DNA synthesis using single molecule PCR. (2008) Nucleic Acids Res 36: e107 (Added 2012-03-11 10:12:12.765491)|
|18654224||Shapiro E, Gil B Biotechnology: logic goes in vitro. (2007) Nat Nanotechnol 2: 84-5 (Added 2012-03-11 10:12:19.919043)|
|18632647||Frumkin D, Wasserstrom A, Itzkovitz S, Stern T, Harmelin A, Eilam R, Rechavi G, Shapiro E Cell lineage analysis of a mouse tumor. (2008) Cancer Res 68: 5924-31 (Added 2012-03-11 10:12:23.750956)|
|18463615||Linshiz G, Yehezkel TB, Kaplan S, Gronau I, Ravid S, Adar R, Shapiro E Recursive construction of perfect DNA molecules from imperfect oligonucleotides. (2008) Mol Syst Biol 4: 191 (Added 2012-03-11 10:12:44.19138)|
|18404205||Wasserstrom A, Frumkin D, Adar R, Itzkovitz S, Stern T, Kaplan S, Shefer G, Shur I, Zangi L, Reizel Y, Harmelin A, Dor Y, Dekel N, Reisner Y, Benayahu D, Tzahor E, Segal E, Shapiro E Estimating cell depth from somatic mutations. (2008) PLoS Comput Biol 4: e1000058 (Added 2012-03-11 10:12:51.767176)|
|18398465||Wasserstrom A, Adar R, Shefer G, Frumkin D, Itzkovitz S, Stern T, Shur I, Zangi L, Kaplan S, Harmelin A, Reisner Y, Benayahu D, Tzahor E, Segal E, Shapiro E Reconstruction of cell lineage trees in mice. (2008) PLoS One 3: e1939 (Added 2012-03-11 10:12:58.305278)|
|18284708||Frumkin D, Wasserstrom A, Itzkovitz S, Harmelin A, Rechavi G, Shapiro E Amplification of multiple genomic loci from single cells isolated by laser micro-dissection of tissues. (2008) BMC Biotechnol 8: 17 (Added 2012-03-11 10:13:12.473821)|
|18039028||Kaplan S, Itzkovitz S, Shapiro E A universal mechanism ties genotype to phenotype in trinucleotide diseases. (2007) PLoS Comput Biol 3: e235 (Added 2012-03-11 10:13:16.489593)|
|16708487||Shapiro E, Benenson Y Tapping the computing power of biological molecules gives rise to tiny machines that can speak directly to living cells. (2006) Sci Am 294: 44-51 (Added 2012-03-11 10:13:20.492116)|
|16261192||Frumkin D, Wasserstrom A, Kaplan S, Feige U, Shapiro E Genomic variability within an organism exposes its cell lineage tree. (2005) PLoS Comput Biol 1: e50 (Added 2012-03-11 10:13:33.413943)|
|15215499||Adar R, Benenson Y, Linshiz G, Rosner A, Tishby N, Shapiro E Stochastic computing with biomolecular automata. (2004) Proc Natl Acad Sci U S A 101: 9960-5 (Added 2012-03-11 10:13:37.932998)|
|15116117||Benenson Y, Gil B, Ben-Dor U, Adar R, Shapiro E An autonomous molecular computer for logical control of gene expression. (2004) Nature 429: 423-9 (Added 2012-03-11 10:13:40.871571)|
|12601148||Benenson Y, Adar R, Paz-Elizur T, Livneh Z, Shapiro E DNA molecule provides a computing machine with both data and fuel. (2003) Proc Natl Acad Sci U S A 100: 2191-6 (Added 2012-03-11 10:13:46.592171)|
|12353013||Regev A, Shapiro E Cells as computation. (2002) Nature 419: 343 (Added 2012-03-11 10:13:50.20392)|