Forster Lab

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Minimal Cell Project

SynBio links above

The Boss!?

Professor Anthony C. Forster, M.D., Ph.D.
University Chair in Chemical Biology
Program Leader, Structural and Molecular Biology
Department of Cell and Molecular Biology
Uppsala University

office and mailing address:
ICM Dept., Room D9:216b
Husargatan 3, Box 596
75124 Uppsala, Sweden

office and cell phone: +46-18-471 4618
e-mail: a.forster(at)icm.uu.se
lab web: http://openwetware.org/wiki/Forster_Lab
Department web: http://www.icm.uu.se/
Uppsala University web: http://www.uu.se/en/

Biography:
Anthony C. Forster (Ph.D. Biochem., U. Adelaide; M.D., Harvard U.) researches RNA, protein synthesis and applications thereof (synthetic biology). He discovered the hammerhead catalytic RNA structure, invented external guide sequences for ribonuclease P, and created unnatural genetic codes de novo, all of which founded biotech companies. He has published in journals including Cell, Nature and Science, edited volumes of Methods and Biotechnology J., and coauthored "Synthetic Biology: A Lab Manual."

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Research Description:
Synthetic biology, protein synthesis and drug discovery
SynBio is a creative new field defined as the complex engineering of replicating systems. It encompasses next-generation technology for bioengineering and fresh approaches to global challenges such as drug discovery and biofuels.
Our current projects include:
1. Improving ribosomal incorporation of unnatural amino acids for investigating translation mechanism and for applications such as directed evolution of peptidomimetic drugs.
2. Metagenomic discovery of antibiotic resistance genes in humans, and overcoming resistance by antisense bacteriophage therapy.
3. Development of chromoproteins for biosensor diagnostics.
4. Simplifying the design and assembly of large genetic pathways and systems.
5. Determining functions of ribosomal RNA modifications towards synthesis of the ribosome, self-replication and a minimal cell.

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Research Keywords:
Synthetic biology, protein synthesis, drug discovery and resistance, antisense phage therapy, minimal genome synthesis, chromoprotein, unnatural amino acid, directed evolution, translation, ribosome, RNA, modification enzyme, E. coli, bacteria, microbiology, biochemistry, Tony Forster

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Meet our lab group:

Minimal Cell Project

phones in lab:
+46-18-471 4387, 471 4651 and 471 4204

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iGEM 2011 Uppsala University Team Members:
http://2011.igem.org/Team:Uppsala-Sweden/Team
Congratulations on qualifying at the European competition in Amsterdam for the world championships at MIT!

iGEM 2012 Uppsala University Team Members:
http://2012.igem.org/Team:Uppsala_University/Team
Congratulations on the top score for a Scandinavian team!

iGEM 2013 Uppsala University Team Members:
http://2013.igem.org/Team:Uppsala
https://www.facebook.com/UppsalaIgem
Congratulations on winning "Best New BioBrick Part, Natural" at the European competition in Lyon and on qualifying for the world championships at MIT!

iGEM 2014 Ravenwood High School Team Members:
http://2014hs.igem.org/Team:Ravenwood_Raptors
Congratulations on being the first iGEM team from Tennessee!

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Teaching:
1MB433: Synthetic Biology (10 hp, weeks 7-12)
http://www.uu.se/en/education/master/selma/kursplan/?kpid=24757&type=1

http://www.worldscientific.com/worldscibooks/10.1142/9061#t=aboutBook

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Postdoctoral Applicants:
Minimal qualifications include expertise in molecular biology and 2 first-authored research papers in international peer-reviewed journals. Experience with bacterial translation or RNA is a plus. Please mail a letter of interest, C.V. and names/e-mail addresses/phone #'s of 3 references.

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Master and PhD Applicants:
Students enrolled in a Master program or with a Master degree are welcome to apply for a few months work experience in the lab. Extension into a PhD position is possible. Research experience is a plus. Please mail a letter of interest, C.V. and names/e-mail addresses/phone #'s of 2 references.

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PATENTS:
Forster, A C, Blacklow, S C. Process and compositions for peptide, protein and peptidomimetic synthesis. US6977150
(founding I.P. for Ra Pharmaceuticals, Inc., Boston).
Altman, S, Forster, A C, Guerrier-Takada, C L. Cleavage of targeted RNA by RNAase P. US5168053
(founding I.P. for Innovir Laboratories, Inc., NY).

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PUBLICATIONS:
Almost all pubs indexed by and available from PubMed:
http://www.ncbi.nlm.nih.gov/pubmed/ (type "Forster AC")
Citations per paper are available from Google Scholar:
http://scholar.google.com/ (type "Forster AC")

Shepherd, T R, Du, L, Liljeruhm, J, Samudyata, Wang, J, Sjödin, M O D, Wetterhall, M, Yomo, T, Forster A C. De novo design and synthesis of a 30-cistron translation-factor module. Nucleic Acids Res, in press, 2017.

Wang, J, Forster A C. Translational roles of the C75 2'OH in an in vitro tRNA transcript at the ribosomal A, P and E sites. Scientific Reports 7, 6709, 1-8, 2017.

Wang, J, Kwiatkowski, M, Forster A C. Ribosomal peptide syntheses from activated substrates reveal rate limitation by an unexpected step at the peptidyl site. J Am Chem Soc 138, 15587-15595, 2016.
Open access reprint: http://pubs.acs.org/articlesonrequest/AOR-zaSQNqqWdhhtNYzkiSwx

Wang, J, Kwiatkowski, M, Forster A C. Kinetics of tRNAPyl-mediated amber suppression in E. coli translation reveals unexpected limiting steps and competing reactions. Biotechnol Bioeng 113, 1552-1559, 2016.

Wang, J, Kwiatkowski, M, Forster A C. Kinetics of ribosome-catalyzed polymerization using artificial aminoacyl-tRNA substrates clarifies inefficiencies and improvements. ACS Chem Biol 10, 2187-2192, 2015.

Kwiatkowski, M, Wang, J, Forster, A C. Facile synthesis of N-acyl-aminoacyl-pCpA for preparation of mischarged fully ribo tRNA. Bioconjugate Chem 25, 2086-2091, 2014.

Liljeruhm, J, Gullberg, E, Forster A C. Synthetic biology: A lab manual. World Scientific Press, 204 pp, 2014. http://www.worldscientific.com/worldscibooks/10.1142/9061#t=aboutBook

Wang, J, Kwiatkowski, M, Pavlov, M Y, Ehrenberg, M, Forster, A C. Peptide formation by N-methyl amino acids in translation is hastened by higher pH and tRNAPro. ACS Chem. Biol. 9, 1303-1311 and front cover, 2014.

Ieong, K-W, Pavlov, M Y, Kwiatkowski, M, Ehrenberg, M., Forster, A C. A tRNA body with high affinity for EF-Tu hastens ribosomal incorporation of unnatural amino acids. RNA 20, 632-643, 2014.

Punekar, A, Liljeruhm, J, Shepherd, T R, Forster, A C, Selmer, M. Structural and functional insights into the molecular mechanism of rRNA m6A methyltransferase RlmJ. Nucleic Acids Res 41, 9537-9548, 2013.

Quax, T E F, Wolf, Y I, Koehorst, J J, Wurtzel, O, van der Oost, R, Ran, W, Blombach, F, Makarova, K S, Brouns, S J J, Forster, A C, Wagner, E G H, Sorek, R, Koonin, E V, van der Oost, J. Differential translation tunes uneven production of operon-encoded proteins. Cell Reports 4, 938-944, 2013.

Ieong, K-W, Pavlov, M Y, Kwiatkowski, M, Forster, A C(corresponding), Ehrenberg, M. Inefficient delivery but fast peptide bond formation of unnatural L-aminoacyl-tRNAs in translation, J Am Chem Soc 134, 17955-17962, 2012.

Punekar, A, Shepherd, T R, Liljeruhm, J, Forster, A C, Selmer, M. Crystal structure of RlmM, the 2'O-ribose methyltransferase for C2498 of E. coli 23S rRNA. Nucleic Acids Res, 40, 10507-10520, 2012.

Forster, A C. Synthetic biology challenges long-held hypotheses in translation, codon bias and transcription. Biotech J, 7, 835-845, 2012.

Forster, A C, Lee, S Y. Editorial: NextGen SynBio has arrived... Biotech J, 7, 827, 2012.

Du, L, Villarreal, S, Forster, A C. Multigene expression in vivo: supremacy of large versus small terminators for T7 RNA polymerase. Biotechnol Bioeng, 109, 1043-1050, 2012.

Wang, H H, Huang P-Y, Xu G, Haas W, Marblestone A, Li J, Gygi S P, Forster A C, Jewett M C, Church G M. Multiplexed in vivo His-tagging of enzyme pathways for in vitro single-pot multienzyme catalysis. ACS Synthetic Biol, 1, 43-52, 2012

Watts, R E, Forster A C. Update on pure translation display with unnatural amino acid incorporation. Methods in Molecular Biology, 805, 349-365, 2012

Gao, R, Forster, A C. Changeability of individual domains of an aminoacyl-tRNA in polymerization by the ribosome. FEBS Lett, 584(1), 99-105, 2010

Jewett, M C, Forster, A C. Update on designing and building minimal cells. Curr Opin Biotech, 21, 697-703, 2010

Watts, R E, Forster, A C. Chemical models of peptide formation in translation. Biochemistry, 49, 2177-2185, 2010

Du, L, Gao, R, Forster, A C. Engineering multigene expression in vitro and in vivo with small terminators for T7 RNA polymerase. Biotechnol Bioeng, 104, 1189-1196, 2009

Forster, A C. Low modularity of aminoacyl-tRNA substrates in polymerization by the ribosome. Nucleic Acids Res, 37, 3747-3755, 2009

Pavlov, M Y, Watts, R E, Tan, Z, Cornish, V W, Ehrenberg, M, Forster, A C. Slow peptide bond formation by proline and other N-alkylamino acids in translation. Proc Natl Acad Sci USA, 106(1), 50-4, 2009

Forster, A C, Church, G M. Synthetic biology projects in vitro. Genome Res, 17(1), 1-6 and front cover, 2007

Zhang, B, Tan, Z, Gartenmann Dickson, L, Nalam, M N L, Cornish, V W, Forster, A C. Specificity of Translation for N-Alkyl Amino Acids. J Am Chem Soc, 129(37), 11316-11317, 2007

Forster, A C, Church, G M. Towards synthesis of a minimal cell. Mol Syst Biol, 2(45), 1-10, 2006

Forster, A C. Engineering translation: A nano-review. Methods, 36(3), 225-6, 2005

Tan, Z, Blacklow, S C, Cornish, V W, Forster, A C. De novo genetic codes and pure translation display. Methods, 36(3), 279-90, 2005

Forster, A C, Cornish, V W, Blacklow, S C. Pure translation display. Anal Biochem, 333(2), 358-64, 2004

Tan, Z, Forster, A C, Blacklow, S C, Cornish, V W. Amino acid backbone specificity of the Escherichia coli translation machinery. J Am Chem Soc, 126(40), 12752-3, 2004

Forster, A C, Tan, Z, Nalam, M N L, Lin, H, Qu, H, Cornish, V W, Blacklow, S C. Programming peptidomimetic syntheses by translating genetic codes designed de novo. Proc Natl Acad Sci USA, 100(11), 6353-7, 2003

Forster, A C, Weissbach, H, Blacklow, S C. A simplified reconstitution of mRNA-directed peptide synthesis: activity of the epsilon enhancer and an unnatural amino acid. Anal Biochem, 297(1), 60-70, 2001

Li, E, Beard, C, Forster, A C, Bestor, T H, Jaenisch, R. DNA methylation, genomic imprinting, and mammalian development. Cold Spring Harb Symp Quant Biol, 58, 297-305, 1993

Forster, A C, Altman, S. External guide sequences for an RNA enzyme. Science, 249(4970), 783-6, 1990

Forster, A C, Altman, S. Similar cage-shaped structures for the RNA components of all ribonuclease P and ribonuclease MRP enzymes. Cell, 62(3), 407-9, 1990

Forster, A C, Davies, C, Hutchins, C J, Symons, R H. Characterization of self-cleavage of viroid and virusoid RNAs. Methods Enzymol, 181, 583-607, 1990

McInnes, J L, Forster, A C, Skingle, D C, Symons, R H. Preparation and uses of photobiotin. Methods Enzymol, 184, 588-600, 1990

Forster, A C, Davies, C, Sheldon, C C, Jeffries, A C, Symons, R H. Self-cleaving viroid and newt RNAs may only be active as dimers. Nature, 334(6179), 265-7, 1988

McInnes, J L, Forster, A C, Symons, R H. Photobiotin-labelled DNA and RNA hybridization probes. Methods in Molecular Biology, 4, 401-414, 1988

Forster, A C, Jeffries, A C, Sheldon, C C, Symons, R H. Structural and ionic requirements for self-cleavage of virusoid RNAs and trans self-cleavage of viroid RNA. Cold Spring Harb Symp Quant Biol, 52, 249-59, 1987

Forster, A C, Symons, R H. Self-cleavage of virusoid RNA is performed by the proposed 55-nucleotide active site. Cell, 50(1), 9-16, 1987

Forster, A C, Symons, R H. Self-cleavage of plus and minus RNAs of a virusoid and a structural model for the active sites. Cell, 49(2), 211-20, 1987

Symons, R H, Hutchins, C J, Forster, A C, Rathjen, P D, Keese, P, Visvader, J E. Self-cleavage of RNA in the replication of viroids and virusoids. J Cell Sci Suppl, 7, 303-18, 1987

Hutchins, C J, Rathjen, P D, Forster, A C, Symons, R H. Self-cleavage of plus and minus RNA transcripts of avocado sunblotch viroid. Nucleic Acids Res, 14(9), 3627-40, 1986

Forster, A C, McInnes, J L, Skingle, D C, Symons, R H. Non-radioactive hybridization probes prepared by the chemical labelling of DNA and RNA with a novel reagent, photobiotin. Nucleic Acids Res, 13(3), 745-61, 1985

Visvader, J E, Forster, A C, Symons, R H. Infectivity and in vitro mutagenesis of monomeric cDNA clones of citrus exocortis viroid indicates the site of processing of viroid precursors. Nucleic Acids Res, 13(16), 5843-56, 1985

Lab pics

UAG