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  • Light Sets the Molecular Controls of Circadian Rhythm | Newswire
    made by the period per and timeless tim genes respectively All cells of the fly have per and tim genes but the brain cells set the body clock PER and TIM proteins accumulate in the nuclei of eye cells sensitive to light called photoreceptors as well as pacemaker cells of the central brain Scientists at the California Institute of Technology discovered per in 1971 while Young s group identified tim in 1994 The fly circadian cycle begins around noon when the per and tim genes transcribe their DNA into RNA molecules essential to create the PER and TIM proteins but only after sunset does the accumulated RNA prompt the cell to stockpile the PER and TIM proteins At night the proteins pair and migrate into the nucleus home to cells genetic material About four hours before dawn the level of PER TIM protein complexes peaks which signals the per and tim genes to stop making RNA and hence the protein complexes Near dawn the PER TIM protein complexes disintegrate With the complexes depleted the per and tim genes begin to make RNA again by midday The scientists found that the TIM and PER proteins need each other to get into the nucleus However if flies are exposed to light one of the proteins TIM rapidly degrades which blocks the movement of the remaining protein to the nucleus In the natural environment even though RNA levels have been rising since midday sunlight keeps TIM protein from accumulating until nightfall explains Young This postponement delays the binding and nuclear activity of the PER and TIM proteins until the night part of the cycle The findings also suggest how light exposure at the different times of day adapts the rhythm such as adjusting to a new time zone For example Young and his

    Original URL path: http://newswire.rockefeller.edu/1996/03/21/light-sets-the-molecular-controls-of-circadian-rhythm/ (2016-02-13)
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  • Eric Siggia joins National Academy of Sciences | Newswire
    and head of the Laboratory of Theoretical Condensed Matter Physics has developed bioinformatics techniques to help process the large amounts of data generated by genomic sequencing He has also developed algorithms and modeling systems to identify regulatory regions of DNA determine binding preferences of transcription factors and shed light on how dividing cells control their size He joined The Rockefeller University in 1997 Eric s work in bioinformatics and modeling has given the scientific community powerful tools for understanding the complexities of biological systems says Paul Nurse the university s president I am extremely pleased that he has been recognized with this prestigious honor The National Academy of Sciences is a private nonprofit honorific society of distinguished scholars engaged in scientific and engineering research dedicated to the furthering of science and technology and to their use for the general welfare Established in 1863 the National Academy of Sciences has served to investigate examine experiment and report upon any subject of science or art whenever called upon to do so by any department of the government The Rockefeller faculty now includes 35 members or foreign associates of the National Academy of Sciences The National Academy of Sciences Tags Eric Siggia newswire

    Original URL path: http://newswire.rockefeller.edu/2009/05/05/eric-siggia-joins-national-academy-of-sciences/ (2016-02-13)
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  • Simulator allows scientists to predict evolution’s next best move | Newswire
    is merely individual random genetic mutations By looking at the series of mutations in evolutionary space Siggia head of the Laboratory of Theoretical Condensed Matter Physics and Paul Francois a postdoc in his lab now provide a computational answer to one of Darwin s biggest questions In this evolutionary space Francois and Siggia instructed their algorithm to find a network that worked very much like an eye after adjusting to different levels of light The eye is a very good example of adaptation says Francois It admits different amounts of light when light levels change and after some period of adjustment your eyes work equally well as before That s what we selected for we instructed our algorithm to find a network that after responding to some input always comes back to its initial value or level of working That s perfect adaptation To find this network the algorithm like Darwinian evolution showed no mercy During each generation the algorithm randomly added deleted or changed the features of genes in a population of gene networks and selected only those that were the most fit and thus most likely to reproduce After duplicating the fittest networks in each generation it repeated the process of mutation selection and duplication over and over again until it eventually arrived at the network that adapted perfectly to a random biochemical input Francois and Siggia found that certain mutations automatically increased a network s fitness and thus were immediately selected When you look at systems like the eye or structures like the human spinal cord you think how could these have evolved from a simple network says Francois In their current study Siggia and Francois looked at how a complex biochemical network could evolve and an answer came together It is built through a specific series

    Original URL path: http://newswire.rockefeller.edu/2008/10/29/simulator-allows-scientists-to-predict-evolutions-next-best-move/ (2016-02-13)
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  • Device allows scientists to control gene activity across generations of cells | Newswire
    a controlled pulse of protein at any time and then see how the cell would respond he says Although scientists have had the tools to track single cells and measure the protein levels within them the new device allows scientists to track them for a longer period of time while not only monitoring but also controlling the activity of genes The precision with which the device can track single cells also allows scientists to construct pedigrees making it possible to compare gene activity from one cell to the next The device relies on electrovalves to control a flow of media which travels through a tube and then diffuses across a porous membrane to reach the budding yeast cells The cells are clamped between this membrane and a soft material which forces them to bud horizontally without damage That was the major design hurdle says Charvin To create a device in which cells don t move so that you can track hundreds of single cells for a long time about eight rounds of cell division which typically lasts 12 hours In order to induce the activity of a gene the researchers used inducer molecules that diffuse through the cell membrane and control DNA segments called promoters The molecule s presence silences the promoter which silences the expression of the gene the molecule s absence on the other hand activates the promoter which activates the gene to crank up the molecule s production By exploiting this principle the scientists showed that they could successfully turn specific genes on and off by controlling the flow of an inducer molecule called methionine They observed that pulses as short as 10 minutes led to changes in protein levels that could be measured The group used this device to study the cell cycle by putting a

    Original URL path: http://newswire.rockefeller.edu/2008/02/28/device-allows-scientists-to-control-gene-activity-across-generations-of-cells/ (2016-02-13)
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  • Sizing cells up: Researchers pinpoint when a cell is ready to reproduce | Newswire
    have identified several key proteins that regulate and play a role in coordinating cell growth and division during G1 they have not been able to get to the core mechanism that senses whether a cell possesses enough resources to divide Scientists needed a way to organize and confidently sort out molecular candidates involved in cell size control from those that played other roles Graduate student Stefano Di Talia a biophysicist and postdoc Jan Skotheim an applied mathematician provided just that Working with Eric Siggia head of the Laboratory of Theoretical Condensed Matter Physics and Fred Cross head of the Laboratory of Yeast Molecular Genetics Di Talia and Skotheim showed that a unique cellular event the exiting of the protein Whi5 from the nucleus separates G1 into two independent steps one controlled by a sizer T1 and one controlled by a timer T2 T1 begins when the mother and daughter cells have completely separated from each other T2 starts in G1 once Whi5 has exited the nucleus and lasts until the new daughter cell forms its own bud You need some way to know how big you are says first author Di Talia whose work appears in the August 23 issue of Nature This precise quantitative framework allows us to narrow down the possibility of events that are involved in size control By measuring the sizes of budding yeast and how long they spend in G1 and in T1 Di Talia saw that daughter cells which are much smaller than their mother cells need to spend more time in T1 growing Once daughter cells reach the required size for division they spend as much time as their mothers in T2 subsequently replicating their DNA and producing daughter cells of their own Di Talia and his colleagues used genetics to show that

    Original URL path: http://newswire.rockefeller.edu/2007/09/20/sizing-cells-up-researchers-pinpoint-when-a-cell-is-ready-to-reproduce/ (2016-02-13)
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  • New ‘PhyloGibbs’ software helps scientists make sense of DNA | Newswire
    made the cell may not function as it should and so the molecules that control how much of a gene is made are of great interest to scientists The computer program called PhyloGibbs which Siggia and Nimwegen developed with former postdoc Rahul Siddharthan builds on previous software designed to identify where these regulatory molecules bind to DNA Like its predecessors PhyloGibbs compares DNA from multiple species in order to identify areas in which the genetic code is statistically similar and filter segments that are most likely to be of interest to scientists This approach however has been complicated by several factors First such inter species conservation of DNA is not always indicative of function in organisms that are closely related evolutionarily some segments of the sequence may be alike simply because the sequences have not diverged sufficiently Second not all functional segments are conserved because many mutations either do not affect function or are compensated for by other mutations To compensate for these drawbacks Siggia and van Nimwegen s software goes a step further After regulatory sequences from the same genes in different organisms are aligned the program searches for the regions that are most likely to function as regulatory sites The algorithm takes into account that binding sites for the same factor will share significant DNA sequences and that functional binding sites are evolutionarily constrained to retain their affinity for the regulatory molecules The program then evaluates each region of the DNA it analyzes for the likelihood that it is a binding site assigning each a score based on the evolutionary relationships between the different species Both conserved sequence blocks and sequence segments unique to a single organism are considered in the search and are scored consistently In this way the code allows multiple sites of multiple types to

    Original URL path: http://newswire.rockefeller.edu/2006/01/04/new-phylogibbs-software-helps-scientists-make-sense-of-dna/ (2016-02-13)
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  • PhyloGibbs | Newswire
    disease there s no shortage of information The challenge is making sense of the data A new algorithm designed by Eric Siggia s Rockefeller laboratory may be an important new tool for scientists seeking to extract answers from sequenced genomes More Tags Eric Siggia PhyloGibbs Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011 more About Contact Follow rockefelleruniv

    Original URL path: http://newswire.rockefeller.edu/tag/phylogibbs/ (2016-02-13)
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  • Noise inner life cells | Newswire
    process by which cells switch on or transcribe genes to make proteins In the same way that chance can lead to long run of lucky dice rolls in a game of craps random fluctuations in the process of transcribing genes may result in unpredictable levels of protein This type of noise is called intrinsic noise But while several mathematical biologists have predicted noisy genes the phenomenon is hard to detect experimentally Elowitz and colleagues figured out a way not only to test this theory in living cells but literally to visualize the results Their trick was to genetically engineer the bacterium E coli to express two identical genes the only difference being that one encodes a protein that glows blue and one yellow these colors were changed to red and green respectively for the sake of image analysis Because both of these genes are in the same cell and thus share the same intracellular environment and because they both are under the control of the same promoter patch of DNA that regulates gene expression they should produce the same amount of protein With both genes making equal amounts of red and green protein the host cell should appear yellow But if noise is inherent to this protein making process one gene may temporarily express higher levels of one protein over the other causing the cell to appear red or green As the mélange of colors in the image above of the genetically altered bacteria shows noise is indeed a part of a cell s inner life Less equals more Why did theorists predict shaky gene expression in the first place The answer is that cells possess relatively few copies of a given protein and an even smaller number of genes For example E coli bacteria have at most a few copies of every gene each one producing an average of only a few tens of proteins per generation To understand why a process involving few molecules would be more susceptible to noise think back to that lucky game of craps A player could feasibly roll an unusually high proportion of lucky sevens and walk away a big winner But if like most people the player gets sucked into the addiction of gambling and continues to play his or her luck would eventually run out In other words chance plays a greater role in a game of craps involving few throws of the dice in the same way that noise should be significant to cells containing a limited number of molecules Elowitz and colleagues put this notion to the test by artificially altering the rate of transcription in their system if noise is indeed dependent upon the number of proteins produced then it should go down as the rate of transcription goes up As expected the researchers observed that noise tapered off as transcription rates went up thereby confirming the theorists original predictions Reason for randomness The next big question is how a cell manages to function properly in the midst

    Original URL path: http://newswire.rockefeller.edu/2002/10/25/noise-inner-life-cells/ (2016-02-13)
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