Biophysics 101 Tasks

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* Choose your favorite human chromosome and paste the URL below: * Choose your favorite human chromosome and paste the URL below:
** Chiki Gupta - [ About Chromosome 22] ** Chiki Gupta - [ About Chromosome 22]
-** Mark Kaganovich -+** Mark Kaganovich - [ Chromosome 20]
** Jason Leith - ** Jason Leith -
** Matthew Meisel - [ Y chromosome] ** Matthew Meisel - [ Y chromosome]

Revision as of 08:04, 8 November 2005

Perl Exercises

  • write a Perl script to read in a DNA sequence from a file and print the following
    • original sequence
    • length of sequence
    • reverse complement (antisense)
    • GC content (%)
    • positions of any EcoRI restriction sites

You can write separate scripts for each task, or put everything in the same script.

Download data from

  • Choose a human chromosome you plan to use (for example, as input for the program in the exercise above)
    • write a perl script that reads the ASCII chromosome data and encodes the chromosome in memory (2 bits per basepair)
    • output this binary description as a file
    • read in the binary description from a file
    • output the ASCII description again
    • convince us your program is correct!

Please work together on the wiki—you do not need to be the sole author of the programs you run—but you should run programs yourself on "your" chromosome.

Papers to review

  • Please take information from this section and move it to your user page (or wherever you feel is appropriate). After you are finished your review (a few paragraphs) be sure to mention what you have done (and where you did it) in your report of weekly activities for the class. Remember to keep Biophysics 101 Background up-to-date also.
  • Feel free to add papers here (for other people to review.)
  • Burgard AP, Pharkya P, Maranas CD. (2003) Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol Bioeng. 2003 Dec 20;84(6):647-57. PDF

The advent of genome-scale models of metabolism has laid the foundation for the development of computational procedures for suggesting genetic manipulations that lead to overproduction. In this work, the computational OptKnock framework is introduced for suggesting gene deletion strategies leading to the overproduction of chemicals or biochemicals in E. coli. This is accomplished by ensuring that a drain towards growth resources (i.e., carbon, redox potential, and energy) must be accompanied, due to stoichiometry, by the production of a desired product. Computational results for gene deletions for succinate, lactate, and 1,3-propanediol (PDO) production are in good agreement with mutant strains published in the literature. While some of the suggested deletion strategies are straightforward and involve eliminating competing reaction pathways, many others suggest complex and nonintuitive mechanisms of compensating for the removed functionalities. Finally, the OptKnock procedure, by coupling biomass formation with chemical production, hints at a growth selection/adaptation system for indirectly evolving overproducing mutants.

  • The International HapMap Consortium (2005) A haplotype map of the human genome Nature 437, 1299-1320 Full text & PDF

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

  • Gibbs R (2005) Deeper into the genome commentary on HapMap milestone and where to go next Full text & PDF

I thought this was nice timing to get the HapMap 1e6 SNP milestone on the cover of Nature. If you review this paper, try to tie it in with the personalized medicine project. To what extent is the HapMap actually complete? How will it fit into the larger picture, or interface with other data? --smd 23:49, 26 October 2005 (EDT)

  • Martin VJ, Pitera DJ, Withers ST, Newman JD, Keasling JD. (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids Nat Biotechnol. Jul;21(7):796-802. Full text & PDF

Not exactly personalized medicine, but a very interesting application of systems and synthetic biology for drug production. Ironically, Jay Keasling will be giving a talk at the ICSB 2005 meeting during class on Thursday, October 20.

Abstract: Isoprenoids are the most numerous and structurally diverse family of natural products. Terpenoids, a class of isoprenoids often isolated from plants, are used as commercial flavor and fragrance compounds and antimalarial or anticancer drugs. Because plant tissue extractions typically yield low terpenoid concentrations, we sought an alternative method to produce high-value terpenoid compounds, such as the antimalarial drug artemisinin, in a microbial host. We engineered the expression of a synthetic amorpha-4,11-diene synthase gene and the mevalonate isoprenoid pathway from Saccharomyces cerevisiae in Escherichia coli. Concentrations of amorphadiene, the sesquiterpene olefin precursor to artemisinin, reached 24 mug caryophyllene equivalent/ml. Because isopentenyl and dimethylallyl pyrophosphates are the universal precursors to all isoprenoids, the strains developed in this study can serve as platform hosts for the production of any terpenoid compound for which a terpene synthase gene is available.

  • Young Chung et al. Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres Nature advance online publication; published online 16 October 2005 | doi: 10.1038/nature04277 Full text & PDF

Abstract: The most basic objection to human embryonic stem (ES) cell research is rooted in the fact that ES cell derivation deprives embryos of any further potential to develop into a complete human being. ES cell lines are conventionally isolated from the inner cell mass of blastocysts and, in a few instances, from cleavage stage embryos. So far, there have been no reports in the literature of stem cell lines derived using an approach that does not require embryo destruction. Here we report an alternative method of establishing ES cell lines—using a technique of single-cell embryo biopsy similar to that used in pre-implantation genetic diagnosis of genetic defects10—that does not interfere with the developmental potential of embryos. Five putative ES and seven trophoblast stem (TS) cell lines were produced from single blastomeres, which maintained normal karyotype and markers of pluripotency or TS cells for up to more than 50 passages. The ES cells differentiated into derivatives of all three germ layers in vitro and in teratomas, and showed germ line transmission. Single-blastomere-biopsied embryos developed to term without a reduction in their developmental capacity. The ability to generate human ES cells without the destruction of ex utero embryos would reduce or eliminate the ethical concerns of many.

see also: Stem Cell Test Tried on Mice Saves Embryo NYT

  • Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease Full text & PDF

Summary: Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD [...], even after adjustments for age, sex, education, follow-up time, locomotor disorders, APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the APOE 4 carriers.

  • Lovley D. Cleaning up with genomics: applying molecular biology to bioremediation. Nature Reviews Microbiology 1, 35-44 (2003); doi:10.1038/nrmicro731 PDF Read and commented upon 18-Oct--Jleith 02:09, 18 October 2005 (EDT)

Abstract: Bioremediation has the potential to restore contaminated environments inexpensively yet effectively, but a lack of information about the factors controlling the growth and metabolism of microorganisms in polluted environments often limits its implementation. However, rapid advances in the understanding of bioremediation are on the horizon. Researchers now have the ability to culture microorganisms that are important in bioremediation and can evaluate their physiology using a combination of genome-enabled experimental and modelling techniques. In addition, new environmental genomic techniques offer the possibility for similar studies on as-yet-uncultured organisms. Combining models that can predict the activity of microorganisms that are involved in bioremediation with existing geochemical and hydrological models should transform bioremediation from a largely empirical practice into a science.

  • Price N, Reed J, Palsson B. Genome-scale models of microbial cells: evaluating the consequences of constraints. Nature Reviews Microbiology 2, 886-897 (2004); doi:10.1038/nrmicro1023 PDF

Abstract: Microbial cells operate under governing constraints that limit their range of possible functions. With the availability of annotated genome sequences, it has become possible to reconstruct genome-scale biochemical reaction networks for microorganisms. The imposition of governing constraints on a reconstructed biochemical network leads to the definition of achievable cellular functions. In recent years, a substantial and growing toolbox of computational analysis methods has been developed to study the characteristics and capabilities of microorganisms using a constraint-based reconstruction and analysis (COBRA) approach. This approach provides a biochemically and genetically consistent framework for the generation of hypotheses and the testing of functions of microbial cells.