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| Keywords: Scenario: Yeast cell-cycle; Model organism; MYSPE | |||||||||||
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Objectives:
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Time management: Before you begin, estimate how long it will take you to complete this unit. Then, record in your course journal: the number of hours you estimated, the number of hours you worked on the unit, and the amount of time that passed between start and completion of this unit. Journal: Document your progress in your Course Journal. Some tasks may ask you to include specific items in your journal. Don’t overlook these. Insights: If you find something particularly noteworthy about this unit, make a note in your insights! page. |
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Evaluation: NA: This unit is not evaluated for course marks. |
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This unit discusses a scenario for model-organism based inference in a (possibly) uncharacterized species and selects a “MYSPE” (My Species), a genome-sequenced fungus that is specific to your explorations in the course.
You have learned about the concept of “cargo cult science(W)”. The “cargo” in Bioinformatics is to understand biology. This includes understanding how things came to be the way they are, and how they work. Both relate to the concept of function of biomolecules, and the systems1 they contribute to. But “function” is a rather poorly defined concept and exploring ways to make it rigorous and computable and explore it from the perspective of “collaborating” components is a major objective of this course. For this, we will work with an example: a transcription factor(W) that plays an important role in the regulation of the cell cycle. This is a relatively well-characterized protein that is part of a relatively well-characterized process. The genetic regulation of budding- and fission yeast cell-cycles has been lucidly described in a highly recommended review by McInerny (2011)2 (see also the short, recent introduction to cell-cycle regulated transcription by McInerny (2016)3). One transcription factor, Mbp1 is a key component of the MBF complex (Mbp1/Swi6) in yeast. This complex regulates gene expression at the crucial G1/S-phase transition of the mitotic cell cycle and has been shown to bind to the regulatory regions of more than a hundred target genes. It is therefore a DNA binding protein that acts as a control switch for a key cellular process, it is highly conserved across species, and its human homologue plays a role in human disease.
Baker’s yeast, Saccharomyces cerevisiae is one of the most important model organisms(W), a eukaryote that has been studied genetically and biochemically in great detail for many decades, and is easily manipulated with high-throughput experimental methods. But model organisms are studied for their value in inferring biology in other, less-well characterized or less experimentally tractable species through computational inference. To implement such a process, you will adopt a different genome-sequenced fungus in which to make discoveries based on knowledge about yeast.
In this unit we will set out on our exploration of the system that regulates the G1/S transition by focussing first on the Mbp1 protein in selected species from the kingdom(W) of fungi, whose genome has been completely sequenced; our quest is thus also an exercise in model-organism reasoning: the transfer of knowledge from one, well-studied species to others. It’s reasonable to hypothesize that such central control machinery is conserved in most if not all fungi. But we don’t know. Many of the species that we will be working with have not been characterized in great detail, and some of them are new to our class this year. And while we know a fair bit about Mbp1, we probably don’t know very much at all about the related genes in other species: whether they exist, whether they have similar functional features and whether they might contribute to the G1/S checkpoint system in a similar way. Thus we might discover things that are new and interesting. This is a quest of discovery.
Since we were trying to find related proteins in a different species, our first task is to find suitable species. Where do these come from? For the purposes of the course “quest”, we need species: * that actually have transcription factors that are related to Mbp1; * whose genomes have been sequenced; and * for which the sequences have been deposited in the RefSeq database, NCBI’s unique sequence collection.
Selecting them is a process that is exemplary for other purposes: define properties that you need in a particular species, and select accordingly. The R-project contains R scripts for this purpose. This is rather detailed code, read through it anyway and make a point of understanding the general workflow of the process in which we retrieve data from different databases, and merge it.
Task…
ABC-units R project. If you
have loaded it before, choose File ▸ Recent
projects ▸ ABC-Units. If you have not loaded
it before, follow the instructions in the RPR-Introduction
unit.init() if requested.BIN-MYSPE.R and follow the instructions.
Note: take care that you understand all of the code in the script. Evaluation in this course is cumulative and you may be asked to explain any part of code.
Task…
If in doubt, ask! If anything about this contents is not clear to you, do not proceed but ask for clarification. If you have ideas about how to make this material better, let’s hear them. We are aiming to compile a list of FAQs for all learning units, and your contributions will count towards your participation marks.
Improve this page! If you have questions or comments, please post them on the Quercus Discussion board with a subject line that includes the name of the unit.
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