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9th EMBL/EMBO Joint Conference 2008

Doron Lancet, Weizmann Institute of Science, Israel

lancet

Doron Lancet

Biography

Doron Lancet is Professor at the Department of Molecular Genetics, Weizmann Institute of Science in Israel. Doron Lancet pioneered genome research in Israel, and currently heads of the Crown Human Genome Center at Weizmann and Israel's National Center for Genomics. He is actively involved in teaching bioinformatics and in initiating a Systems Biology effort at the Weizmann Institute. A pioneer of olfactory research, he currently studies the genomics and population genetics of human olfaction, as well as the evolution of the olfactory receptor superfamily.

He developed GeneCards, a widely used web-based human gene compendium, and also does research in transcriptomics and pharmacogenetics. More recently, he initiated a program addressing computational models for life's origins on earth, with direct implications to synthetic biology. Lancet is member of EMBO and a HUGO council member. Prof. Lancet wrote a science column in the major Israeli daily Haaretz, and continuously delivers public lectures on the present and future impact of the Genome Project.

Abstract

Diversity: a driving force for life's inception and synthesis

One of the greatest challenges of synthetic biology is to chemically engineer a simplified self-reproducing system. Even the simplest of such systems, obtained by a top-down approach, i.e. by gradually simplifying present-day living cells, appears to be irrevocably complex. Therefore, a bottom-up approach is more appropriate if Synthetic Biology's declared goal of combining science and engineering in synthetizing novel biological functions and systems is to be followed. Self reproduction comes in two different flavors: one is the ability of individualmolecules, such as DNA and RNA to generate their own copies. Indeed, many Synthetic Biology efforts rely on this unique attribute, attempting to develop and utilise molecular replicators such as a self-copying ribozyme. The other reproduction flavor is the capacity of entire cells to fission and form progeny. In our laboratory we take the latter route, and ask how a cell-like reproducing system can emerge from diverse collections of molecules. Because present-day test-tube biochemistry is rather limited, we resort to computer simulations, with the view that in a few decades it will be possible to emulate in-silico practically evey aspect of chemistry.

This approach echoes new developments in the realm of Systems Chemistry, a joint effort of prebiotic and supramolecular chemistry, as well as theoretical biology and complex systems research to address problems relating to the origin and synthesis of life. The "Lipid world" prebiotic scenario we have proposed considers assemblies of relatively simple molecules, held together by weak, nonspecific forces. Such assemblies may be readily formed spontaneously, either in the primordial soup or in a present-day laboratory. The crucial question is how diversity and mutual interactions are translated, in some cases, to a capacity to undergo self-reproduction, hence selection and evolution. An important feature of our proposed scenario is the notion that molecular assemblies may store and propagate compositional information. This has precedence in present-day cells, which prior to division have to augment their molecular repertoires under strict condition of compositional preservation. To examine the detailed dynamics of a potential process of compositional reproduction, we use a computer-simulated artificial chemistry formalism, the Graded Autocatalysis Replication Domain (GARD) model. The rare compositional states capable of reproduction-like dynamic behavior ("composomes") are shown to undergo mutation-like events, leading to a simple evolutionary progression. The Lipid World / GARD concepts could complement other Synthetic Biology attempts to embody self reproduction in a man-made chemical system.