BCIG SPEAKER EVENT: "Synthetic Gene Design: Motivation, Chellenges and Progress"

Clinical Center (Building 10) Medical Board Room (Room 2C116)

DESCRIPTION: An increasingly common challenge of molecular biology is to move genes from their 'natural' genomic context into a 'foreign' (heterologous) context for subsequent manipulation and/or expression of their protein product. It was largely assumed that challenges here were purely technical: once gene manipulation was easy and cheap, the existence of a standard genetic code should ensure straightfoward success for heterologous expression experiments. The reality is now recognized as a highly heterogeneous mixture of sucess and failures. One of the key elements emerging as a possible confounding factor concerns codon bias: the "spelling preferences" that different genomes exhibit in their unequal usage of synonymous codons. Here I will discuss some of the work of my graduates in exploring this phenomenon, from the analysis of "rules for success" to the contruction of a dedicated database of "synthetic genes".

3:00 - 4:30 pm May 18, 2006

LAST MINUTE CANCELLATION

Unfortunately, Steve Freeland had
transportation problems and this talk will have to be rescheduled!

Stephen J. Freeland
University of Maryland Baltimore County

FACULTY POSITION
Aug 2001-present
Assistant Professor, Dept Biological Sciences, University of Maryland Baltimore County (UMBC).
At UMBC, I lead a research lab of Ph.D., Masters’ and undergraduate students in developing an interactive web of bioinformatics tools for genome exploration and analysis. The toolkit uses (and extends) evolutionary theory surrounding the origin and evolution of the genetic code to explore and understand the genomic ‘subtext’ of coding sequences.

POST-DOCTORAL RESEARCH EXPERIENCE June 2001-Aug 2001 John Templeton Foundation summer support, Dept. EEB, Princeton University. (co-PI with Prof. Laura Landweber)
Summer support to pursue investigations of chance and chemical determinism in the evolution of the genetic code. This grant has funded supervision of an undergraduate research project to investigate the plausibility of reconstructing the ancestral form of biosynthetic enzymes that are purported to have ‘invented’ new amino acids during the early evolution of life.

June 1999-June 2001 HFSP (Human Frontiers Science Program) Fellow, Dept. EEB, Princeton University. (supervisor: Prof. Laura Landweber)
A two year collaborative research program investigating the evolution of the genetic code, and the subsequent implications for molecular evolution. This fellowship has involved a diverse combination of research initiatives, from the development and use of special analysis software, through statistical analysis to laboratory synthesis of predicted gene sequences for functional experiments within E coli.

Nov. 1998-June 1999 DIMACS Fellowship, Dept. EEB, Princeton University. (supervisor: Prof. Laura Landweber)
A six month post-doctoral fellowship laying the groundwork for a collaborative research program into the origin and evolution of the genetic code. Lead to a major review paper on theories of code evolution, and the launch of novel software development, sequence analysis and literature reviews to synthesise current information about code evolution.

Related Links

PUBLICATIONS TO DATE
(2006) "On the evolution of the standard amino-acid alphabet" ~ Lu Y and Freeland SJ. Genome Biology, 7:102.
(in press) "Simplified Gene Synthesis: A one-step approach to PCR-based gene construction" ~ (In Press) G. Wu, J.B. Wolf1, A.F. Ibrahim, S. Vadasz, M. Gunasinghe, S.J. Freeland. J. of Biotechnology.
(in press) "The Synthetic Gene Designer: a flexible web platform to explore sequence manipulation for heterologous expression" ~ (In Press) Wu G, Bashir-Bello N., Freeland SJ. Protein Expression and Purification.
(2004) "The standard genetic code enhances adaptive evolution of proteins" ~ (2006) Zhu W and Freeland S.J., Journal of Theoretical Biology. 239(1) 63-70. (2004) "Evolution Encoded" S.J. Freeland and L. Hurst, Scientific American 290:84-91.
(2003) "Three Fundamentals of the Biological Genetic Algorithm" S.J. Freeland, in Genetic Programming Theory and Practice, eds. Riolo R and Worzel B., Kluwer Academic.
(2003) "The case for an Error Minimizing Standard Genetic Code", S.J. Freeland, T. Wu and N. Keulmann, Origins of Life and Evolution of the Biosphere 33: 457-477.
(2002) “The triplet genetic code: key to living organisms”, (invited book review), S.J. Freeland. Heredity 89: 236-237
(2002) “The genetic code: an adaptation for adapting?”, S.J. Freeland. Journal of Genetic Programming and Evolvable Machines, 3(2): 113-127.
(2001) “A simple model based on mutation and selection explains trends in codon and amino-acid usage and GC composition within and across genomes”, R.D. Knight, S.J. Freeland and L.F. Landweber, Genome Biol. 2(4):RESEARCH0010.
(2001) “Genview and Gencode: a pair of programs to test adaptation within the genetic code”, T.A. Ronneberg, S.J. Freeland and L.F. Landweber, Bioinformatics, 17(3):280-1.
(2001) “Testing a biosynthetic theory of genetic code evolution: fact or artefact?”, T.A. Ronneberg, L.F. Landweber and S.J. Freeland, Proc. Natl. Acad. Sci. USA, 97(25):13690-5
(2001) “Rewiring the keyboard: evolvability of the genetic code”, R.D. Knight, S. J. Freeland and L. F. Landweber, Nature Reviews Genetics, 2(1):49-58.
(2000) “Early Fixation of an Optimal Genetic Code”, S.J. Freeland, R.D. Knight, L.F. Landweber and L.D. Hurst. Mol. Biol. Evol.,17 pp. 511-518.
(2000) "Measuring adaptation within the genetic code", S.J. Freeland, R.D. Knight and L.F. Landweber, Trends Biochem. Sci. 25 pp. 44-45.
(1999) "Do Proteins Predate DNA?", S.J. Freeland, R.D. Knight, L.F. Landweber, Science, 286, pp. 690-692.
(1999) "The 3 Faces of the Genetic Code", R.D. Knight, S. J. Freeland and L. F. Landweber, Trends Biochem. Sci. 282(24), pp. 241-247
(1998) "The genetic code is one in a million", S.J. Freeland and L.D. Hurst, Journal of Molecular Evolution, 47(3), pp. 238-248.
(1998) "Load minimisation of the genetic code: History does not explain the pattern", S.J. Freeland and L.D. Hurst, Proc. Roy. Soc. Lond. B, 265, pp 2111-2119.
(1997) "Fitness compensation and the evolution of selfish cytoplasmic elements", S.J. Freeland and B.K. McCabe, Heredity 78 pp. 391-402.