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-- SijieMao - 15 Sep 2008

  1. Ensure that your home page includes a photo and a short piece of biographical text, as outlined in the lab. choice-yes.gif
  2. Give two examples of how computational biology is relevant to synthetic biology.
    • Bioinformatics; identification of sequence patterns in databases in order to predict functions of genes or to identify genes that follow a particular pattern to be used as parts in synthetic biology.
    • Structure Models; use of algorithms to predict/analyze the 3D structure of a biomolecule and determine the energetics of its interactions and chemical activity
  3. What is the difference between a virus and a transposon? Give a technological application of each. Discuss possible physical limitations on the design of modified viruses and/or transposons.
    • A biological virus is able to move to and infect new host cells whereas a transposon can only move about in the genome of a host.
    • Biological viruses can be used as vectors for gene therapies, such as in targeting and killing cancer cells. Transposons can be used to introduce mutations into organisms, such as the P elements in Drosophila.
    • Modified viruses can trigger an immune reaction from a host and be destroyed, may only infect certain cells, and may mutate in a way that they lose their original effectiveness or change to potentially dangerous behavior over time. Modified transposons may trigger an immune reaction ie: RNAi and be destroyed, they move around in the host genome every generation and change so that mutations aren't consistent, and they are only inherited through the germ-line and therefore cannot move to other cells in the first generation organism.
  4. Using Google, Wikipedia and any other relevant sources, write a short description (1-4 sentences) of the following types of tool (including programs and databases) that are used in bioinformatics. Mention the main biological purpose or typical application of the tool, and name prominent examples of each type of tool. Each type of tool comes in a pair: as an integral part of your description, compare and contrast the two tools in the pair(touch on key issues that are encountered with using the tools in practice, e.g. accuracy, run-time, memory usage, etc.)
    • Protein Structure Prediction
      • Ab initio protein structure prediction software(ie: ROBETTA, Rosetta@Home, CABS) builds 3D protein models based on physical principles by modeling protein folding and using stochastic methods.
      • Comparative protein structure modeling software(ie: MODELLER, SwissModel) builds 3D protein models based on previously solved structures, based on the idea that there are a limited number of possible protein folds and structure motifs.
        • The two tools are based on different approaches to predicting protein structures(sequence vs. experimental).
    • Gene Function
      • Controlled vocabularies for gene/enzyme function (ie: EC numbers, the Gene Ontology project, EpoDB) are key terms and their definitions used to describe gene functions. They are intended to limit the variation in terminology used in scientific papers/databases, allowing searches to be more efficient/effective.
      • Biochemical pathway databases(ie: BioPath, MetaCyc, KEGG PATHWAY, Reactome) is a collection of information about the network of interactions and the pathway/sequence of transformations that occurs between biomolecules involved in metabolism/cellular processes.
        • Both tools organize data in order for it to be more accessible/searchable, by categorizing genes/biochemicals by their function or by their role in a specific biological process.
    • Structure Analysis
      • Protein/protein docking software(ie: RosettaDock, HADDOCK, DOT) models the structure of protein-protein complexes in order to predict whether proteins will bind, binding affinity and how one is oriented based on the other ie: in order to predict the activity of a protein and the effects of mutations.
      • Protein/small-molecule docking software(ie: Affinity, AutoDock, eHiTS) models the structure of protein-small-molecule complexes in order to predict activity and affinity to targets ie: in designing drugs.
        • Protein/protein docking models protein/protein interactions while protein/small-molecule docking models the activating/inhibiting action of small molecules on a protein.
    • Sequence Analysis
      • Sequence assembly software(ie: Celera Assembler, Arachne and AMOS) aligns sequence fragments(ie: from shotgun sequencing of a genome or ESTs) and merges them in order to assemble a complete sequence. Problems include sequencing larger genomes and more complex organisms, repeats and errors caused by the sequencing process.
      • Gene-finding software(ie: GeneMark, GLIMMER, GENSCAN, CONTRAST) finds functional sequences(genes)in DNA (ie: identifying protein, RNA-coding sequences, or regulatory sequences in a genome) by identifying regulatory elements/other recurring characteristics or comparing sequences to known protein/mRNA sequences. Problems include the complexity of eukaryotic genes and their regulatory elements and splicing.
        • Sequence assembly is necessary to put together sequences while gene-finding is involved in the analysis the sequence once it has been assembled.
    • RNA structure
      • RNA folding software(ie: ViennaRNA, UNAFold, mFold) predicts secondary structures of RNA based on minimizing the free energy of the structure ie: to predict the function of an RNA or how it will interact.
      • RNA design software(ie: RNA Designer, siDirect) designs RNA sequences according to a desired secondary structure in order to obtain a desired structure and ultimately, a desired function ie: to make ribozymes and self-assembling RNAs, RNA interference.
        • RNA folding attempts to solve the sequence to structure problem while RNA design is the reverse, attempting to design a sequence for a desired structure.
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