Forster Lab

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(The Boss!?)
(The Boss!?)
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{{Synthetic biology top}}
{{Synthetic biology top}}
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<div style="padding: 10px; color: #000000; background-color: #ccccff; width:730px" >
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[[Image:Tony Forster003.jpg|thumb|right|Minimal Cell Project]]
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[[Image:Tony Forster003.jpg|450px|right|Minimal Cell Project]]
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[[Image:Frankenstein's Creature.JPG|thumb|right|Synthetic Tony Forster]]
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SynBio links above<br><br>
SynBio links above<br><br>
== The Boss!? ==
== The Boss!? ==
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Husargatan 3, Box 596<br>
Husargatan 3, Box 596<br>
75124 Uppsala, Sweden<br><br>
75124 Uppsala, Sweden<br><br>
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phone: 46-18-471 4618<br>
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phone: +46-18-471 4618<br>
e-mail: a.forster@icm.uu.se<br>
e-mail: a.forster@icm.uu.se<br>
lab web: http://openwetware.org/wiki/Forster_Lab<br>
lab web: http://openwetware.org/wiki/Forster_Lab<br>
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<font color="green">'''Group Members:'''</font><br>
<font color="green">'''Group Members:'''</font><br>
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Anthony C. Forster, M.D., Ph.D.<br>
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Anthony C. Forster, M.D., Ph.D. (principal investigator)<br>
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Marek Kwiatkowski, Ph.D.<br>
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Raymond Fowler (laboratory technician)<br>
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Josefine Liljerum<br>
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Marek Kwiatkowski, Ph.D. (senior researcher)<br>
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Sofia Ny<br>
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Josefine Liljeruhm (doctoral student)<br>
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Samudyata (sole name)<br>
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Sofia Ny (project student)<br>
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Tyson R. Shepherd, Ph.D.<br>
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Tyson R. Shepherd, Ph.D. (Wenner-Gren postdoctoral fellow)<br>
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Andreas Svahn<br>
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Andreas Svahn (project student)<br>
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Jinfan Wang<br>
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Jinfan Wang (doctoral student)<br>
<br>
<br>
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phones in lab: 46-18-471 4204 and 4870<br>
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phones in lab: +46-18-471 4387, 4651 and 4204<br>
<br>
<br>
<font color="green">'''iGEM 2011 Uppsala University Team Members:'''</font><br>
<font color="green">'''iGEM 2011 Uppsala University Team Members:'''</font><br>
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Congratulations on qualifying at the European competition in Amsterdam for the world championships at MIT!<br>
Congratulations on qualifying at the European competition in Amsterdam for the world championships at MIT!<br>
<br>
<br>
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<font color="green">'''iGEM 2012 Uppsala University Team Members:'''</font><br>
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http://2012.igem.org/Team:Uppsala_University<br>
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Congratulations on the top score for a Scandinavian team!<br><br>
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'''Postdoctoral Position:'''<br>
'''Postdoctoral Position:'''<br>
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'''Research Keywords:'''<br>
'''Research Keywords:'''<br>
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Synthetic biology, Protein synthesis, RNA, Unnatural amino acid, Directed evolution, Ribosome, mRNA, tRNA, E.coli, Engineering, Tony Forster, Anthony Forster, Anthony C. Forster, A. C. Forster,Bacteria,Biochemistry,Cancer,Enzyme action,Genome,Genomics,Microbiology,Pharmacology,Post-transcriptional modification,Transcription termination,Translation
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Synthetic biology, protein synthesis, drug discovery, directed evolution, translation, unnatural amino acid, ribosome, RNA, mRNA, tRNA, codon bias, E. coli, bacteria, microbiology, biochemistry, modification enzyme, transcription termination, Tony Forster, Anthony Forster, A. C. Forster
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'''[[Research Description:]]'''<br>
'''[[Research Description:]]'''<br>
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2. Can cell-free protein production be improved to rival inherently less-flexible in vivo systems?<br>
2. Can cell-free protein production be improved to rival inherently less-flexible in vivo systems?<br>
3. What genes are required to completely reconstitute translation (the "translatome")?<br>
3. What genes are required to completely reconstitute translation (the "translatome")?<br>
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4. Can new protein synthesis inhibitors be developed to combat rising bacterial resistance?<br>
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4. What are the functions of ribosomal RNA modifications?<br>
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5. Can new protein synthesis inhibitors be developed to combat rising bacterial resistance?<br>
Ironically, in addition to being a target for antibiotic development, we envisioned that the translation apparatus could also be engineered to generate drug leads against translation or any other target molecules.
Ironically, in addition to being a target for antibiotic development, we envisioned that the translation apparatus could also be engineered to generate drug leads against translation or any other target molecules.
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'''PATENTS:'''<br>
'''PATENTS:'''<br>
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Forster, A C, Blacklow, S C. Process and compositions for peptide, protein and peptidomimetic synthesis. US6977150.<br>
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Forster, A C, Blacklow, S C. Process and compositions for peptide, protein and peptidomimetic synthesis. US6977150<br>
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Altman, S, Forster, A C, Guerrier-Takada, C L. Cleavage of targeted RNA by RNAase P. US5168053.
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(founding I.P. for Ra Pharmaceuticals, Inc., Boston).<br>
 +
Altman, S, Forster, A C, Guerrier-Takada, C L. Cleavage of targeted RNA by RNAase P. US5168053<br>
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(founding I.P. for Innovir Laboratories, Inc., NY).<br>
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'''PUBLICATIONS:'''<br>
'''PUBLICATIONS:'''<br>
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Links available via your institutional account at PubMed<br>
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Almost all pubs indexed by and available from PubMed<br>
http://www.ncbi.nlm.nih.gov/pubmed/ (type "Forster AC")
http://www.ncbi.nlm.nih.gov/pubmed/ (type "Forster AC")
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Ieong, K-W, Pavlov, MY, Kwiatkowski, M, Forster, AC* and Ehrenberg, M. Submitted manuscript on incorporation of unnatural amino acids in translation.
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Ieong, K-W, Pavlov, MY, Kwiatkowski, M, Ehrenberg, M. and Forster, AC, Manuscript on improving incorporation of unnatural L-aminoacyl-tRNAs in translation.
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Punekar, A, Shepherd, TR, Liljeruhm, J, Forster, AC and Selmer, M. Nucleic Acids Res, manuscript on ribosome biogenesis accepted subject to revision.
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Ieong, K-W, Pavlov, MY, Kwiatkowski, M, Forster, AC(corresponding author) and Ehrenberg, M., Inefficient delivery but fast peptide bond formation of unnatural L-aminoacyl-tRNAs in translation, J Am Chem Soc, published online.
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Forster, AC and Lee, SY. Editorial: NextGen SynBio has arrived... Biotech J, 7, in press, 2012.
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Punekar, A, Shepherd, TR, Liljeruhm, J, Forster, AC and 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.
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Forster, AC. Synthetic biology challenges long-held hypotheses in translation, codon bias and transcription. Biotech J, 7, published online, 2012.
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Forster, AC. Synthetic biology challenges long-held hypotheses in translation, codon bias and transcription. Biotech J, 7, 835-845, 2012.
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Forster, AC and Lee, SY. Editorial: NextGen SynBio has arrived... Biotech J, 7, 827, 2012.
Du, L, Villarreal, S, Forster, AC. Multigene expression in vivo: supremacy of large versus small terminators for T7 RNA polymerase. Biotechnol Bioeng, 109, 1043-1050, 2012.
Du, L, Villarreal, S, Forster, AC. Multigene expression in vivo: supremacy of large versus small terminators for T7 RNA polymerase. Biotechnol Bioeng, 109, 1043-1050, 2012.
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== Lab pics ==
== Lab pics ==
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[[Image:Forster_lab_members_2011.jpg|800px|left]]
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[[Image:Lab_group_activities.jpg|730px|left]]
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[[Image:Golf scramble.jpg|800px|left]]
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[[Image:Forster_lab_members_2011.jpg|730px|left]]
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[[Image:Pharmacology lake retreat.jpg|800px|left]]
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[[Image:Forster lab warming, 2005.jpg|730px|left]]
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[[Image:Mammoth Cave excursion.jpg|800px|left]]
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[[Image:Forster lab warming, 2005.jpg|800px|left]]
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UAG
UAG

Revision as of 15:29, 25 November 2012

Home        About        Conferences        Labs        Courses        Resources        FAQ       

Minimal Cell Project

SynBio links above

The Boss!?

Professor Anthony C. Forster, M.D., Ph.D.
University Chair in Chemical Biology
Program in 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

phone: +46-18-471 4618
e-mail: a.forster@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/


Group Members:
Anthony C. Forster, M.D., Ph.D. (principal investigator)
Raymond Fowler (laboratory technician)
Marek Kwiatkowski, Ph.D. (senior researcher)
Josefine Liljeruhm (doctoral student)
Sofia Ny (project student)
Tyson R. Shepherd, Ph.D. (Wenner-Gren postdoctoral fellow)
Andreas Svahn (project student)
Jinfan Wang (doctoral student)

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

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
Congratulations on the top score for a Scandinavian team!


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


Research Keywords:
Synthetic biology, protein synthesis, drug discovery, directed evolution, translation, unnatural amino acid, ribosome, RNA, mRNA, tRNA, codon bias, E. coli, bacteria, microbiology, biochemistry, modification enzyme, transcription termination, Tony Forster, Anthony Forster, A. C. Forster


Research Description:
SYNTHETIC BIOLOGY, PROTEIN SYNTHESIS AND DRUG DISCOVERY:
Synthetic biology is a new field that may be defined as the complex engineering of replicating systems ( http://syntheticbiology.org/ ). Protein synthesis is central to this field and also to antibiotic development. Important questions remain unanswered. For example,
1. What are the mechanisms of substrate recognition and peptide bond formation?
2. Can cell-free protein production be improved to rival inherently less-flexible in vivo systems?
3. What genes are required to completely reconstitute translation (the "translatome")?
4. What are the functions of ribosomal RNA modifications?
5. Can new protein synthesis inhibitors be developed to combat rising bacterial resistance?
Ironically, in addition to being a target for antibiotic development, we envisioned that the translation apparatus could also be engineered to generate drug leads against translation or any other target molecules.


WHERE WE ARE:
We've reconstituted a simplified, purified translation system that has enabled:
1. Modular alteration of aminoacyl-tRNA substrates using chemical synthesis to reveal key elements for substrate function in translation,
2. Overturning of dogma on the rate-limiting step in translation,
3. Explaining why the genetic code evolved to contain proline,
4. Creation of rudimentary genetic codes de novo, and
5. Genetic screening of a model library of polypeptides in a purified system, termed "pure translation display."
6. Proposed a list of genes essential for reconstitution of translation (a "minimal translatome") and have begun synthesizing and testing the genes using "BioBricks", revealing unexpected properties of transcription terminators.


WHERE WE'RE GOING:
We aim to exploit our purified translation system to:
1. Determine the rules of substrate recognition by the translation apparatus,
2. Enable ligand discovery using pure translation display of peptides containing multiple, protease-resistant, unnatural amino acids,
3. Synthesize active 23 rRNA in vitro using rRNA modification enzymes associated with antibiotic resistance,
4. Optimize in vitro translation systems,
5. Determine the genes necessary for reconstitution of translation, and
6. Synthesize a life-like replicating system (a minimal cell project) dependent only on small molecules for food.


EDUCATION:
B.Sc.Hons., University of Adelaide, Australia
Ph.D., Biochemistry, University of Adelaide, Australia (discovered hammerhead ribozyme structure).
M.D., Harvard University.
Residency, Anatomical Pathology, Brigham and Women's Hospital, Boston.


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).


PUBLICATIONS:
Almost all pubs indexed by and available from PubMed
http://www.ncbi.nlm.nih.gov/pubmed/ (type "Forster AC")

Ieong, K-W, Pavlov, MY, Kwiatkowski, M, Ehrenberg, M. and Forster, AC, Manuscript on improving incorporation of unnatural L-aminoacyl-tRNAs in translation.

Ieong, K-W, Pavlov, MY, Kwiatkowski, M, Forster, AC(corresponding author) and Ehrenberg, M., Inefficient delivery but fast peptide bond formation of unnatural L-aminoacyl-tRNAs in translation, J Am Chem Soc, published online.

Punekar, A, Shepherd, TR, Liljeruhm, J, Forster, AC and 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, AC. Synthetic biology challenges long-held hypotheses in translation, codon bias and transcription. Biotech J, 7, 835-845, 2012.

Forster, AC and Lee, SY. Editorial: NextGen SynBio has arrived... Biotech J, 7, 827, 2012.

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

Wang, HH, Huang P-Y, Xu G, Haas W, Marblestone A, Li J, Gygi SP, Forster AC, Jewett MC, Church GM. Multiplexed in vivo His-tagging of enzyme pathways for in vitro single-pot multienzyme catalysis. ACS Synthetic Biology, 1, 43-52, 2012

Watts, RE, Forster AC. Update on pure translation display with unnatural amino acid incorporation. Methods in Molecular Biology, 805, 349-365, 2012

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

Jewett, MC, Forster, AC. Update on designing and building minimal cells. Current Opinion in Biotechnology, 21, 697-703, 2010

Watts, RE, Forster, AC. Chemical models of peptide formation in translation. Biochemistry, 49, 2177-2185, 2010

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

Forster, AC. Low modularity of aminoacyl-tRNA substrates in polymerization by the ribosome. Nucleic Acids Res, 37, 3747-3755, 2009 PMCID:2699524

Pavlov, MY, Watts, RE, Tan, Z, Cornish, VW, Ehrenberg, M, Forster, AC. Slow peptide bond formation by proline and other N-alkylamino acids in translation. Proc Natl Acad Sci U S A, 106(1), 50-4, 2009 PMCID:2629218

Forster, A C, Church, G M. Synthetic biology projects in vitro. Genome Res, 17(1), 1-6, 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 PMCID:2275119

Forster, A C, Church, G M. Towards synthesis of a minimal cell. Mol Syst Biol, 2(45), 1-10, 2006 PMCID:1681520

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 U S A, 100(11), 6353-7, 2003 PMCID:164450

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 plus and minus RNAs of a virusoid and a structural model for the active sites. Cell, 49(2), 211-20, 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

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 PMCID:339804

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 PMCID:341032

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 PMCID:321916

Lab pics

UAG
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