BIN-MYSPE
MYSPE (My Species)
(Scenario: Yeast cell-cycle; Model organism, MYSPE)
Abstract:
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.
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Objectives:
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Outcomes:
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Deliverables:
Prerequisites:
You need the following preparation before beginning this unit. If you are not familiar with this material from courses you took previously, you need to prepare yourself from other information sources:
- Biomolecules: The molecules of life; nucleic acids and amino acids; the genetic code; protein folding; post-translational modifications and protein biochemistry; membrane proteins; biological function.
This unit builds on material covered in the following prerequisite units:
Contents
Evaluation
Evaluation: NA
Contents
Scenario
You have learned about the concept of "cargo cult science". 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 systems[1] 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 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.
Model organism and MYSPE
Baker's yeast, Saccharomyces cerevisiae is one of the most important model organisms, 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 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.
Choosing MYSPE (My Species)
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:
- Open RStudio and load the
ABC-unitsR 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. - Choose Tools → Version Control → Pull Branches to fetch the most recent version of the project from its GitHub repository with all changes and bug fixes included.
- Type
init()if requested. - Open the file
BIN-MYSPE.Rand 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:
- Search for the article on MYSPE on Wikipedia https://wikipedia.org/wiki/Special:Search to learn more about the species.
- Navigate to the NCBI genomes database at https://www.ncbi.nlm.nih.gov/genome , search for MYSPE and read about the status of and motivation for genome work with MYSPE.
Notes
- ↑ cf. the Systems Concepts unit
- ↑
McInerny (2011) Cell cycle regulated gene expression in yeasts. Adv Genet 73:51-85. (pmid: 21310294) [ PubMed ] [ DOI ] The regulation of gene expression through the mitotic cell cycle, so that genes are transcribed at particular cell cycle times, is widespread among eukaryotes. In some cases, it appears to be important for control mechanisms, as deregulated expression results in uncontrolled cell divisions, which can cause cell death, disease, and malignancy. In this review, I describe the current understanding of such regulated gene expression in two established simple eukaryotic model organisms, the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. In these two yeasts, the global pattern of cell cycle gene expression has been well described, and most of the transcription factors that control the various waves of gene expression, and how they are in turn themselves regulated, have been characterized. As related mechanisms occur in all other eukaryotes, including humans, yeasts offer an excellent paradigm to understand this important molecular process.
- ↑
McInerny (2016) Cell cycle regulated transcription: from yeast to cancer. F1000Res 5:. (pmid: 27239285) [ PubMed ] [ DOI ] Recent studies have revealed exciting new functions for forkhead transcription factors in cell proliferation and development. Cell proliferation is a fundamental process controlled by multiple overlapping mechanisms, and the control of gene expression plays a major role in the orderly and timely division of cells. This occurs through transcription factors regulating the expression of groups of genes at particular phases of the cell division cycle. In this way, the encoded gene products are present when they are required. This review outlines recent advances in our understanding of this process in yeast model systems and describes how this knowledge has informed analysis in more developmentally complex eukaryotes, particularly where it is relevant to human disease.
About ...
Author:
- Boris Steipe <boris.steipe@utoronto.ca>
Created:
- 2017-08-05
Modified:
- 2020-09-20
Version:
- 1.1
Version history:
- 1.1 2020 revisions - new workflow
- 1.0 First live version
- 0.1 First stub
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