User:Juedwang

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=== Personal ===
=== Personal ===
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Hi.. my name is Jade.  I am a postdoctoral associate in the [[Grossman Lab]] at [http://web.mit.edu MIT].  I will join [http://imgen.bcm.tmc.edu/molgen/ Baylor College of Medicine] the fall of 2006.
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Hi.. my name is Jade.  I am a postdoctoral associate in the [[Grossman Lab]] at [http://web.mit.edu MIT].  I will set up my own lab in [http://imgen.bcm.tmc.edu/molgen/ Baylor College of Medicine] the fall of 2006.
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=== Contact ===
=== Contact ===
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=== Education ===
=== Education ===
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I learnt biochemistry in grad school.  I worked in the [http://www.ucsf.edu/jswlab/ Weissman Lab] in [http://www.ucsf.edu UCSF].  My graduate work is described [http://online.itp.ucsb.edu/online/bionet03/weissman/oh/01.html here].
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I learnt biochemistry in grad school.  I worked in the [http://www.ucsf.edu/jswlab/ Weissman Lab] at [http://www.ucsf.edu UCSF].  My graduate work is described [http://online.itp.ucsb.edu/online/bionet03/weissman/oh/01.html here].
Before this, I studied physics at McGill University in Canada.
Before this, I studied physics at McGill University in Canada.
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=== Research ===
=== Research ===
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All organisms possess mechanisms to faithfully replicate their DNA.  Replication is highly regulated to minimize errors that could lead to cell death or tumorigenesis.  How do cells avoid mistakes during DNA replication?  How is DNA replication coordinated with cellular processes such as growth and division?  How is replication responsive to external cues such as nutrient availability?  These are important unresolved questions which we are addressing using the bacterium Bacillus subtilis.
 
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B. subtilis displays relative simpler mode of replication comparing to eukaryotes, and is convenient for genetic, genomic, quantitative and systematic analyses.  Understanding universal principles of regulating DNA replication helps us to understand causes for genetic diseases and cancer.  More importantly, the replication machine of B. subtilis is closely related to many microbial pathogens but is dramatically different from eukaryotes.  Studying how B. subtilis replicates helps us to find ways to produce useful antimicrobial drugs that target DNA replication of these pathogens.
 
[[Image:replicationforks.jpg|600px]]
[[Image:replicationforks.jpg|600px]]
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'''Current and future projects:'''
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All organisms must faithfully replicate their DNA to minimize errors that could lead to cell death or decreased fitnessHow do cells avoid mistakes during DNA replication? How is DNA replication coordinated with cellular processes such as growth and division? How is replication responsive to external cues such as nutrient availability?  These are important unresolved questions which my lab will address using the Gram-positive bacterium Bacillus subtilis. B. subtilis has a simpler mode of replication compared to eukaryotes, and is amenable to genetic, genomic, quantitative and systematic analyses. Understanding universal principles of regulating DNA replication helps us to understand causes of genetic diseases and cancer.
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'''Characterize a pathway that regulates replication elongation.''' I have found a novel mechanism for nutritional regulation of DNA replication. Upon starvation, the small nucleotide ppGpp rapidly and directly inhibits B. subtilis primase. We will combine genetics and biochemistry to illustrate the molecular mechanism of this inhibition.
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'''Evaluate the contribution of regulating replication elongation to maintaining genomic stability.''' Replication arrest caused by adverse situations often leads to replication fork collapse.  I found that ppGpp-mediated replication arrest does not lead to such disruption, suggesting that ppGpp could be part of a checkpoint pathway that monitors nutrient availability and regulates replication.  This regulation might help to minimize disruption to replication forks.  We will monitor the survival, mutation, and DNA damage response of cells when this control is abolished.
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'''Investigate the state of arrested replication forks in the middle of a chromosome and the events that lead to replication restart.'''  We will use fluorescence microscopy to visualize the cellular localization of various replication and repair proteins.  To characterize the binding of these proteins to the chromosome, we will conduct ChIP-Chip analysis (chromosome immunoprecipitation-microarrays).
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'''Explore how replication shapes genomic organization.''' In B. subtilis, transcription of the majority of genes (75%) co-orients with replication.  I monitored replication of B. subtilis mutants with re-arranged genomes, and found that head-on transcription impedes replication, while co-orientation of transcription minimizes this impediment. We will use evolutionary and genetic approaches to further examine the nature of the selective pressure to co-orient replication with transcription.
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I have employed genomic microarray techniques and characterized a novel mechanism for regulation of replication elongation by nutrient availability in B. subtilisUpon amino acid starvation, the small nucleotides (p)ppGpp rapidly and directly inhibit B. subtilis primase, an essential component of the replication machineryRegulation of elongation could potentially limit DNA damage caused by uncontrolled replication under unfavorable environments, and help to maintain genomic stability.  My lab will combine genetics and biochemistry to elucidate the molecular mechanism of this inhibition. We will also examine whether this regulation might help to minimize disruption to replication forks, by monitoring the survival, mutation, and DNA damage response of cells when this regulation is abolished.  In addition, we will investigate the state of arrested replication forks in the middle of a chromosome and the events that lead to replication restart.
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Finally, the organization of bacterial genomes helps to reduce problems of replication.  The majority of genes in bacterial genomes co-orient with replication and I found that this co-orientation bias of transcription and replication promotes smooth replication fork progression on a genomic scale. My lab will use genomic and genetic approaches to further examine the nature of the selective pressure that leads to the evolution of co-orientation.
=== Publications ===
=== Publications ===

Current revision

Contents

Personal

Hi.. my name is Jade. I am a postdoctoral associate in the Grossman Lab at MIT. I will set up my own lab in Baylor College of Medicine the fall of 2006.

Contact

wang dot jue at gmail dot com


Education

I learnt biochemistry in grad school. I worked in the Weissman Lab at UCSF. My graduate work is described here.

Before this, I studied physics at McGill University in Canada.

Research

All organisms must faithfully replicate their DNA to minimize errors that could lead to cell death or decreased fitness. How do cells avoid mistakes during DNA replication? How is DNA replication coordinated with cellular processes such as growth and division? How is replication responsive to external cues such as nutrient availability? These are important unresolved questions which my lab will address using the Gram-positive bacterium Bacillus subtilis. B. subtilis has a simpler mode of replication compared to eukaryotes, and is amenable to genetic, genomic, quantitative and systematic analyses. Understanding universal principles of regulating DNA replication helps us to understand causes of genetic diseases and cancer.

I have employed genomic microarray techniques and characterized a novel mechanism for regulation of replication elongation by nutrient availability in B. subtilis. Upon amino acid starvation, the small nucleotides (p)ppGpp rapidly and directly inhibit B. subtilis primase, an essential component of the replication machinery. Regulation of elongation could potentially limit DNA damage caused by uncontrolled replication under unfavorable environments, and help to maintain genomic stability. My lab will combine genetics and biochemistry to elucidate the molecular mechanism of this inhibition. We will also examine whether this regulation might help to minimize disruption to replication forks, by monitoring the survival, mutation, and DNA damage response of cells when this regulation is abolished. In addition, we will investigate the state of arrested replication forks in the middle of a chromosome and the events that lead to replication restart.

Finally, the organization of bacterial genomes helps to reduce problems of replication. The majority of genes in bacterial genomes co-orient with replication and I found that this co-orientation bias of transcription and replication promotes smooth replication fork progression on a genomic scale. My lab will use genomic and genetic approaches to further examine the nature of the selective pressure that leads to the evolution of co-orientation.

Publications

Wang, J.D., Berkmen, M.B., Grossman, A.D. Genome-wide co-orientation of replication and transcription reduces adverse effects on replication in Bacillus subtilis. submitted.

Wang, J.D., Sanders G.M., Grossman, A.D. Nutritional control of elongation of DNA replication by (p)ppGpp. submitted.

Goranov, A.I., Kuester-Schoeck, E., Wang, J.D., Grossman, A.D. (2006) Characterization of the global transcriptional responses to different types of DNA damage and disruption of replication in Bacillus subtilis. J. Bacteriol. 188(15):5595-605.

Wang, J.D., Rokop, M.E., Barker, M.M., Hanson, N.R., Grossman, A.D. (2004) Multicopy plasmids affect replisome positioning in Bacillus subtilis. J. Bacteriol. 186(21):7084-90.

Wang, J.D., Herman, C., Tipton, K.A., Gross, C.A., Weissman, J.S. (2002) Directed evolution of substrate-optimized chaperonins. Cell, 111(7):1027-39.

Wang, J.D., Weissman, J.S. (1999) Thinking outside the box: new insights into the mechanism of GroEL-mediated protein folding. Nature Structural Biology, 6(7): 597-600.

Wang, J.D., Michelitsch, M.D., and Weissman, J.S. (1998) GroEL-GroES-mediated protein folding requires an intact central cavity. Proc. Natl. Acad. Sci. USA, 95 (21): 12163-8.

Johnson, B.L., Sachrajda, A.S., Feng, Y., Taylor, R.P., Kirczenow, G., Henning, L., Wang, J., Zawadzki, P., Coleridge, P.T. (1995) The quantum Hall effect and inter-edge state tunneling within a barrier, Phys. Rev. B 51, 7650.

Kirczenow, G., Sachrajda, A.S., Feng, Y., Taylor, R.P., Henning, L., Wang, J., Zawadzki, P., Coleridge, P.T. (1994) Artificial impurities in quantum wires: from classical to quantum behavior, Phys. Rev. Lett. 72, 2069.

Sachrajda, A.S., Feng, Y., Taylor, R.P., Kirczenow, G., Henning, L., Wang, J., Zawadzki, P., Coleridge, P.T. (1994) Magnetoconductance of a nanoscale anti-dot, Phys. Rev. B, 50, 10856.

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