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  • Scientists develop a tool to study deadly parasite’s histone code | Newswire
    sleeping sickness The advance marks the first time scientists have been able to develop the tools to map these changes across the entire genome of the evolutionarily ancient parasite Histones in trypanosomes are extraordinarily divergent from histones in other organisms so we couldn t use the same commercially available antibodies we use for mammals and yeast to isolate them and study their modifications says Cross If we were interested in histone modifications we couldn t reliably predict which amino acids in the histone tails would be modified and had a role in transcription We now have the means to do that Two years ago Cross and his colleagues were the first to identify histone modifications that exist in T brucei focusing on modifications that occur on H4 one of the four pairs of core histones Building off that research Siegel was able to create an antibody specific to the modified histone whose 10th amino acid was acetylated When the antibody was exposed to the trypanosome genome it attached to the modified histones allowing Siegel to extract them along with the DNA coiled around them from the parasite s nucleus What I had was all these DNA fragments which I could then map back to the genome and see every location where this modification occurred says Siegel The results were striking This modification of H4 occurred along every probable transcription start site across the trypanosome genome suggesting that this modification serves as a loading dock for transcription factors The team proposes that at these transcription start sites H4 s tail is acetylated which helps open up chromatin to make room for factors that initiate transcription Siegel then decided to repeat the procedure for every histone variant in trypanosomes each core histone has one variant revealing that two of them occur at

    Original URL path: http://newswire.rockefeller.edu/2009/05/13/scientists-develop-a-tool-to-study-deadly-parasites-histone-code/ (2016-02-13)
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  • George A.M. Cross | Newswire
    genome wide study scientists are the first to map the epigenetic changes that are likely to play a role in the molecular origami of transcription initiation in Trypanosoma brucei the deadly single celled parasite responsible for African sleeping sickness More Tags African sleeping sickness George A M Cross histone code April 15 2009 Science News Parasite breaks its own DNA to avoid detection The parasite Trypanosoma brucei which causes African sleeping sickness is like a thief donning a disguise Every time the host s immune cells get close to destroying the parasite it escapes detection by rearranging its DNA and changing its appearance Now researchers at Rockefeller University reveal how the parasite initiates its getaway by cleaving both strands of its DNA More Tags African sleeping sickness F Nina Papavasiliou George A M Cross January 29 2007 Science News DNA breaks may help parasites elude the immune system Changing their appearance helps many pathogens hide from detection In the parasite Trypanosoma brucei surface proteins recognized by the host s immune system may be altered by the same process that repairs broken DNA The key lies in T brucei s variant surface glycoproteins which coat the parasite s surface More Tags

    Original URL path: http://newswire.rockefeller.edu/tag/george-a-m-cross/ (2016-02-13)
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  • Parasite breaks its own DNA to avoid detection | Newswire
    the parasite changes its surface coat When the telomeres become critically short they predicted a break occurs in or adjacent to the actively transcribed VSG gene and triggers a switch Based on the observations we made in 2007 we predicted that doubled stranded DNA breaks were behind the switch but we were not able to prove it says Dreesen who is now at the Institute of Medical Biology in Singapore But that all changed when F Nina Papavasiliou head of the Laboratory of Lymphocyte Biology and Catharine Boothroyd a postdoc in Papavasiliou s lab began collaborating with Dreesen and Cross who is André and Bella Meyer Professor at Rockefeller Nina and Catharine had the perfect system to address whether this model was correct or not says Dreesen They had developed a greatly improved assay to measure switching frequency which is incredibly important but what was key was that they were able to artificially put breaks upstream of the active VSG gene and see whether or not the surface coat changed By working with a DNA cleaving enzyme from yeast the team found that a DNA break in a specific region upstream of the active VSG gene causes the parasite to increase its coat switching frequency by 250 times During this break induced recombination a VSG gene from another chromosome is duplicated and then displaces the previously active VSG gene That was an exciting find says Boothroyd because duplicative gene conversion is the way trypanosomes in the wild also switch their surface coats As Boothroyd points out it is also how antibody producing cells called B lymphocytes chop up and rearrange their DNA in order to destroy the virtually limitless number of foreign invaders that can infect us In order for duplicative gene conversion to occur the team found that the

    Original URL path: http://newswire.rockefeller.edu/2009/04/15/parasite-breaks-its-own-dna-to-avoid-detection/ (2016-02-13)
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  • DNA breaks may help parasites elude the immune system | Newswire
    these glycoproteins at a time and switching between them helps T brucei outwit the immune system Variant surface glycoproteins can be switched in a number of ways says George A M Cross the André and Bella Meyer Professor and head of the Laboratory of Molecular Parasitology There are about 20 sites within the parasite s genome that control variant surface glycoprotein expression Transcription can be shifted from one to another or a variant surface glycoprotein gene that isn t being transcribed can be copied to an active expression site in a process called duplicative gene conversion says Cross To understand how trypanosomes accomplish this conversion postdoctoral associate Oliver Dreesen made mutant parasites that lacked the telomerase protein Telomerase is normally essential for the maintenance of telomeres specialized areas of DNA located at the ends of chromosomes and adjacent to variant surface glycoprotein expression sites In the absence of telomerase telomeres would become shorter each time the cells divided and most of the cells would be expected eventually to die After waiting through more than two years of continuous cultivation until the telomeres became critically short it was found that the telomeres at short silent expression sites were unexpectedly stabilized in the absence of the machinery that is normally responsible for their maintenance At the active expression sites however short telomeres were more vulnerable to breakage and variant surface glycoprotein genes were gradually lost and then replaced through duplicative gene conversion events that also replaced the telomeres We suspect that at short telomeres truncations may fall in regions of the DNA just under the telomeres which results in strand breakage says Cross To repair the break the template can be taken from any neighboring subtelomeric site resulting in a new variant surface glycoprotein That new protein in turn alters T brucei

    Original URL path: http://newswire.rockefeller.edu/2007/01/29/dna-breaks-may-help-parasites-elude-the-immune-system/ (2016-02-13)
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  • t. brucei | Newswire
    parasite Trypanosoma brucei surface proteins recognized by the host s immune system may be altered by the same process that repairs broken DNA The key lies in T brucei s variant surface glycoproteins which coat the parasite s surface More Tags African sleeping sickness George A M Cross t brucei Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011

    Original URL path: http://newswire.rockefeller.edu/tag/t-brucei/ (2016-02-13)
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  • “Outlaw” organism turns informant | Newswire
    their own genetic information into a usable form called mRNA by a process called cis splicing Cis refers to a process of splicing together informational cassettes exons that are separated by non coding introns on the same piece of RNA to make a readable transcript This process works like a tightly safeguarded library the cassettes master versions always stay in the library Copies circulate via mRNA Trypanosome genetic material is different in content and in form Trypanosome genes contain no introns and therefore do not need to cis splice their RNA to decode its information The process is closer to what we observe in bacterial transcription says Gopal But trypanosome genes all lack a small piece at their start which is apparently needed for mRNA to be translated into protein and this mini exon has to be added to the RNA in a process called trans splicing When attempting to decode a DNA sequence computers use relatively simplistic methods that cannot say for certain what is a real gene and what stretch of sequence just coincidentally looks like a gene If trans splicing is required for mRNA in trypanosomes identifying DNA signals that specify trans splicing sites can help discriminate real genes from others that are predicted by the computer to be possible genes To this end Gopal developed a system that classifies different kinds of splice signal data Her goal was to learn how to predict trans splicing signals This has involved her in cycles of computer prediction and experimental confirmation Each cycle improves the veracity of the predictive algorithm Gopal in her bioinformatics to bench research focuses on the genetic material at the middle of T brucei s many chromosomes 11 essential plus hundreds of mini chromosomes Another trypanosome researcher at Rockefeller primarily is concerned with what occurs at the ends of these chromosomes Bibo Li a new research assistant professor in Cross s lab who completed a postdoctoral fellowship with Titia de Lange in her Laboratory of Cell Biology and Genetics studies the ends of trypanosome chromosomes called telomeres Telomeres in trypanosomes turn out to have the closest biochemical lettering that is A C T and G organization of nucleotides found in DNA to our own human telomeres As a rich source of insight on chromosomal aging and instabilities leading to cancer telomeres have been an important basic research topic Rockefeller s de Lange a leader in the telomere field conducted her own graduate work on telomeres in T brucei Li s tenure in the Cross lab has only begun but the research she undertakes will illuminate more than one set of biomedical problems By identifying proteins that act on telomeres she will potentially contribute to further understanding of cancer onset and its possible treatments She can conduct endogenous gene experiments in T brucei that cannot be done in humans and reap the benefit of the parasite s rapid reproduction cycle In addition learning more about trypanosome telomere function could reveal a vulnerability in the parasite s

    Original URL path: http://newswire.rockefeller.edu/2002/11/25/outlaw-organism-turns-informant/ (2016-02-13)
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  • Scientists identify DNA that regulates antibody production | Newswire
    close to chromosome ends which makes altering their local sequence especially difficult Instead of tampering with enhancers in place Wesley Dunnick a professor at the University of Michigan Medical School devised a way to move the entire locus the enhancers along with adjacent antibody genes that contain information about foreign invaders onto an artificial bacterial chromosome Placement on the artificial chromosome allows for the modification of the excised locus with relative ease using tools pioneered at Rockefeller by Peter Model and Nathaniel Heintz Dunnick could delete or mutate enhancer sequences at will He then re inserted these modified chromosomes into the mouse Like a bubble floating in the genome these artificial chromosomes would land randomly onto the mouse genome and get incorporated into it now allowing him to study the effect of these modified enhancers on the generation of antibodies In response to the unlimited number of foreign antigens bits of microbes chemicals and other substances that can invade our bodies the immune system must be able to tailor make an unlimited number of antibodies However the amount of DNA in a cell is limited so antibody producing B cells must mutate and re arrange their antibody genes to step up to the challenge using processes called somatic hypermutation and class switch recombination respectively In collaboration with the Papavasiliou lab Dunnick discovered that mice carrying the artificial chromosomes with the antibody genes behave in ways that are indistinguishable from unmanipulated mice they recombine and mutate their antibody genes to generate highly specific attacks on foreign invader But for that they absolutely need their enhancers without them the cell s machinery can transcribe and translate the antibody genes but can t rearrange or mutate them suggesting that the enhancers function as a loading dock for a common initiator molecule which is

    Original URL path: http://newswire.rockefeller.edu/2009/11/19/scientists-identify-dna-that-regulates-antibody-production/ (2016-02-13)
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  • Peter Model | Newswire
    need to be specially sculpted to attack them head on New research now shows that gene segments called enhancers control the reshuffling of antibody genes that makes such a precise and coordinated attack possible More Tags F Nina Papavasiliou Laboratory of Lymphocyte Biology Nathaniel Heintz Peter Model Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011 more About Contact

    Original URL path: http://newswire.rockefeller.edu/tag/peter-model/ (2016-02-13)
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