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  • Duke University Department of Molecular Genetics & Microbiology
    these obligate intracellular bacterial pathogens manipulate host cellular functions to replicate disseminate and ultimately cause disease Chlamydia trachomatis resides within a membrane bound compartment inclusion From this location the pathogen manipulates the actin cytoskeleton microtubule based motors inhibits lysosomal recognition of the inclusion activates signaling pathways re routes lipid transport and prevents the onset of programmed cell death Remarkably all of these functions are achieved with a genome that encodes

    Original URL path: http://mgm.duke.edu/faculty/valdivia/ (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    chlamydiae a group of intracellular bacteria that is related to the important human and animal pathogenic chlamydiae yet infects a wider range of host species including also invertebrates and protozoa In a project supported by the Austrian Academy of Sciences Doc fFORTE fellowship I demonstrated that the acquisition of anti apoptotic activities i e the ability to block programmed cell death in infected cells was a key step during the evolutionary adaptation of chlamydiae to animal hosts My PhD work furthermore challenged the long lasting assumption that the infective developmental stage of chlamydiae the elementary body is metabolically inert and provided first evidence for a link between metabolic activity and infectivity in chlamydiae Yet many questions remained unresolved in part due to the genetic intractability of chlamydiae that has been a major challenge to the study of this group of bacteria until very recently In October 2013 I moved to North Carolina During my post doctoral research in the group of Dr Raphael Valdivia I aim to contribute to the further development of newly established genetic techniques for the analysis of chlamydiae and I aim to apply these techniques to obtain deeper insights into the interaction of the sexually transmitted human pathogen Chlamydia trachomatis with its host cell Publications Sixt BS Kostanjšek R Mustedanagic A Toenshoff ER Horn M 2013 Developmental cycle and host interaction of Rhabdochlamydia porcellionis an intracellular parasite of terrestrial isopods Environ Microbiol doi 10 1111 1462 2920 12252 Sixt BS Siegl A Müller C Watzka M Wultsch A Tziotis D Montanaro J Richter A Schmitt Kopplin P Horn M 2013 Metabolic features of Protochlamydia amoebophila elementary bodies a link between activity and infectivity in chlamydiae PLoS Pathog 9 8 e1003553 Sixt BS Hiess B König L Horn M 2012 Lack of effective anti apoptotic activities restricts

    Original URL path: http://mgm.duke.edu/faculty/valdivia/lab/sixt.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    BS in Pre Medicine from Saint Augustine s College in Raleigh NC in 2005 I took two years off to work in a clinical lab in Duke University Hospitals before realizing I wanted to do research I then went on to pursue an MS in Biology at North Carolina Central University where I studied a novel heat shock gene l 2 dtl and the role it plays as a cell

    Original URL path: http://mgm.duke.edu/graduate/students/sloan.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    DSBs This is accomplished through the use of substrates with engineered single nucleotide polymorphisms SNPs at 50 bp intervals Strand exchange generates mismatch containing heteroduplex DNA hetDNA the length and position of which can be determined by sequencing recombination products The position of hetDNA in individual recombinants can be used to infer the underlying molecular mechanism of recombination Alterations in hetDNA patterns in defined mutant backgrounds provide molecular detail that cannot be obtained using more traditional methods Our molecular analyses have confirmed for example that most mitotic recombination occurs via the synthesis dependent strand annealing pathway and have clarified how individual helicases regulate recombination outcome The basic framework for mapping hetDNA was developed using a transformation based assay in which a broken plasmid is repaired using a SNP containing chromosomal template More recent work has employed chromosomal substrates one of which contains a inducible DSB and has confirmed basic hetDNA patterns observed in the transformation based assay To complement analysis of DSB initiated recombination substrates are being developed that will allow the molecular features of recombination initiated either spontaneously or by a defined single strand nick to be ascertained Finally computational tools are being developed to sequence recombination events en masse using the high throughput single molecule PacBio platform Transcription and genome stability Because the DNA metabolic processes of transcription replication recombination and repair are not temporally separated one process has the potential to influence the occurrence of another Our work has demonstrated that the stability of DNA is related not only to its primary sequence but also is influenced by its level of transcription Reporters fused to the highly inducible pGAL or doxycycline regulated pTet promoter have been used to study how transcription locally stimulates mutagenesis a phenomenon referred to as transcription associated mutagenesis or TAM We have discovered

    Original URL path: http://mgm.duke.edu/faculty/robertson/index.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    John Wyrick studying chromatin and telomeric silencing in yeast Directly after graduation I was hired on as a lab tech for Dr William Davis also of WSU to study the DNA Damage Response in various histone mutants as well as to help with the day to day running of the lab Both were amazing experiences that prepared me very well for graduate studies here at Duke I was drawn to

    Original URL path: http://mgm.duke.edu/faculty/luftig/lab/price.html (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    EBNA 2 are the core transforming oncogenes These proteins are capable of driving B cell proliferation and act to suppress the apoptotic response induced by aberrant S phase induction The goals of the laboratory include i understanding the host pathways that respond to and suppress EBV mediated growth transformation ii understanding the viral gene products important for activating the oncogenic stress response and ultimately overcoming this response and iii identifying

    Original URL path: http://mgm.duke.edu/faculty/luftig/index.htm (2014-06-13)
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  • The Garcia-Blanco Lab
    addition I seek to investigate the mechanisms by which dengue virus utilizes these host factors to promote its own replication This work will further our understanding of dengue virus replication at the molecular level and may lead to the development of anti viral therapies Publications Phillips S L Cygnar D Thomas A and Bresnahan W A Interaction between the human cytomegalovirus tegument proteins UL94 and UL99 is essential for virus replication J Virol 86 18 9995 10005 Phillips S L and Bresnahan W A 2011 The human cytomegalovirus tegument protein UL94 is essential for secondary envelopment J Virol 86 5 2523 32 Phillips S L and Bresnahan W A 2011 Identification of binary interactions between human cytomegalovirus virion proteins J Virol 85 1 440 7 Kronemann D Hagemeier S R Cygnar D Phillips S and Bresnahan W A 2010 Binding of the human cytomegalovirus HCMV tegument protein UL69 to UAP56 URH49 is not required for efficient replication of HCMV J Virol 84 18 9649 54 Hussong S Kapphahn R Phillips S Maldonado M and Ferrington D A 2010 Immunoproteasome deficiency alters retinal proteasome s response to stress J Neurochem 113 6 1481 90 Ianzini F Domann F E Kosmacek E A Phillips S L and Mackey M A 2007 Human glioblastoma U87MG cells transduced with a dominant negative p53 TP53 adenovirus construct undergo radiation induced mitotic catastrophe Radiat Res 168 2 183 92 Ianzini F Bertoldo A Kosmacek E A Phillips S L and Mackey M A 2006 Lack of p53 function promotes radiation induced mitotic catastrophe in mouse embryonic fibroblast cells 2006 Cancer Cell Int 6 1 11 Klingelhutz A J Qian Q Phillips S L Gourronc F A Darbro B W Patil S R 2005 Amplification of the chromosome 20q region is associated with expression of HPV 16

    Original URL path: http://mgm.duke.edu/faculty/garcia/lab/lab/phillips.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    American West Nile virus epidemic and recent Dengue outbreaks in France and the US Comparatively little is known about the molecular biology of these viruses and the Garcia Blanco laboratory is identifying host factors both insect and human required for infection with pathogenic flaviviruses using en masse approaches Given that these viruses live in an RNA world never using DNA as genetic material many of these host factors are RNA binding proteins The work on flaviviruses is carried out at Duke University School of Medicine and at the Duke NUS Graduate Medical School in Singapore 2 Alternative splicing regulation during epithelial mesenchymal transitions in cancer In the great majority of human transcripts protein coding information is found in short exons that are identified and ligated together in the process known as pre messenger RNA splicing The complex nature of genes provides for versatility of expression because one gene can encode for many proteins by altering the selection of exons to be included in the messenger This process is known as alternative splicing and it is the major engine of proteome diversity in humans The laboratory has pioneered the use of reporter constructs to image alternative splicing decisions in vivo both in normal tissues in transgenic mice and in syngeneic prostate tumors in rats In the latter system imaging of alternative splicing has led to the unexpected discovery of epithelial plasticity epithelial mesenchymal and mesenchymal epithelial transitions in tumors presumed to be anaplastic These transitions appear to be essential for tumor progression and the development of metastases the major cause of morbidty and mortality in cancer patients This has led to a reevaluation of the importance of a plasticity phenotype in tumor fitness A major focus of the laboratory is the determination of the signaling pathways that mediate alternative splicing changes

    Original URL path: http://mgm.duke.edu/faculty/garcia/index.htm (2014-06-13)
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