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yeast as a model organism

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josephine slifirski

on 25 October 2014

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Transcript of yeast as a model organism

We already know that yeast plays an integral role in our food industry
What are Yeast?
Unicellular eukaryotic fungi
Characterised as single cells that divide by budding (Saccharomyces)
Commonly used to ferment the sugars of rice, wheat, barley, and corn to produce alcoholic beverages and to expand dough

Advantages of using
Saccharomyces cerevisiae
as a model organism
(Basically, yeast is the best!!)
Disadvantages
Relevance - in terms of phylogeny, humans and yeast are far apart!
It is a small, unicellular organism
It has no brain
BUT did you know it's also a model organism?
yeast as a model organism
How far removed are we from yeast?
The fact that YEAST are unicellular limits what we can use them for
Humans have more than 200 different types of cells, each serving different functions, while yeast are made up of one type of cell...
YEAST have no brain
This limits their role in studies into
psychiatric disorders

ADHD
Schizophrenia
Parkinson's disease
Alzheimer's disease
Future prospects
Important orthologues have not
yet been found in yeast
BUT we can get around this
problem by genetic manipulation
 Tau
 APP
 A-synuclein
 FUS
 TDP-43
 Huntingtin

History of
S. cerevisiae
6000 BCE
– Beer making began in the Fertile Crescent of Sumaria
3000 BCE
– Egyptians and Babylonians utilized fermentation of wild yeast to make bread
1680
– Yeast first visualised by Antoni van Leeuwenhoek using high quality lenses
1815
- Joseph-Louis Gay-Lussac developed methods to maintain grape juice in an unfermented state

Louis Pasteur's Yeast
In 1860, Pasteur proved that fermentation is caused by living organisms and asserted that the agents which are responsible for the reaction are connected with the yeast cell. He then showed that yeast can live with or without oxygen, multiplying in the first case, causing a fermentation in the second case
Øjvind Winge: The Father of Yeast Genetics
(1886 – 1964)
Discovered that yeast spores are diploid and haploid cells occur as a result of conjugation of two haploid cells or self-diploidisation

Traits of yeast are mainly governed by simple Mendelian inheritance

Yeast as a model genetic organism
“as a model for all eukaryotic biology derives from the facility with which the relation between gene structure and protein function can be established”

(Botstein and Fink 1988)

L.H. Hartwell’s Yeast
Leland H. Hartwell, using baker’s yeast, identified the fundamental role of checkpoints in cell cycle control, and CDC genes, which controls the start of the cycle -- the progression through G1

Yeast – a Nobel Prizewinner
2001
– L.H. Hartwell, Paul Nurse & Tim Hunt

2006
– Roger Kornberg for his studies on the first step of gene expression, by which a genes DNA sequence is copied into mRNA

2009
– Elizabeth Blackburn, Carol Greider & Jack Szostak ‘How chromosomes are protected by telomeres and the enzyme telomerase’

2013
– James Rothman, Randy Schekman, and Thomas Südhof  discovered the genes responsible for cargo delivery in S. cerevisiae

It is simply practical to use yeast!
Simple to grow
Replicates rapidly
High progeny numbers
Easy to maintain
Super cheap to purchase and to dispose of
Very compact = easy storage
Can be frozen for later date
Genetically manipulated easily
Studied in a haploid state
New genomic technologies have been validated and still are with the use of yeast! Eg. Microarrays
No ethics approval required
Complete genome sequence available since 1996


When is yeast most useful?
Ideal for researching cellular processes concerned with:
DNA repair mechanisms
Cell cycle checkpoints
As mitochondrial models
Organelle research
Protein processing and secretion

Human v.s. Yeast
1985- Inviable yeast lacked RAS1 and RAS2 genes.
Their viability could be restored upon the introduction of the HRAS human gene in the yeast genome= yeast and human proteins have significant functional similarities

Function of 85% of the genes found in baker’s yeast now known.

Almost 1000 Saccharomyces genes are orthologs of humans genes that have been known to cause disease.
The study of human genetics with the use of yeast
Hereditary nonpolyposis colorectal cancer (HNPCC)
Cause: Incorrect DNA repair.
Human tumors contained DNA repeats
Yeast with this similar mutation was isolated
In 1993 it was concluded that the MSH2 mutated gene found in yeast was the ortholog causative gene in humans known as hMSH2


Yeast great model for studying complex inheritance patterns
Function of its gene products have been well documented
Genes highly conserved and can therefore be compared to our similarly conserved genes

Databases available
Saccharomyces Genome Database (SGD)
http://www.yeastgenome.org
Central hub for newest research and technology utilizing yeast

Saccharomyces Genome Deletion Project
http://www-sequence.stanford.edu/group/yeast_deletion_project/deletions3.html
Almost complete set of every possible open reading frame deletion was produced for yeast= deletion library

Gene Ontology Consortium
http://geneontology.org
web based data space describing known proteins and their functions in a non-species dependent manner

References
ALBA-LOIS, L. & KISCHINEVSKY, C. 2010. Beer & Wine Makers. Nature Education, 3, 9.

BOTSTEIN, D. & CHERVITZ, S. A. 1997. Yeast as a model organism.(similar proteins encoded in yeasts and mammals). Science, 277, 1259.

BOTSTEIN, D. & FINK, G. R. 2011. Yeast: an experimental organism for 21st century biology.(Essay)(Author abstract). Genetics, 189, 695.

MELL, J, C. & BURGESS, S, M. 2002. Yeast as a Model Genetic Organism. Encyclopedia of Life Sciences, 1-8.

MIJALJICA, D., PRESCOTT, M. & DEVENISH, R. J. 2012. A Late Form of Nucleophagy in Saccharomyces cerevisiae (Late Nucleophagy in Yeast). PLoS ONE, 7, e40013.

OSTERGAARD, S., OLSSON, L. & NIELSEN, J. 2000. Metabolic Engineering of Saccharomyces cerevisiae. Microbiology and Molecular Biology Reviews, 64, 34.

PRAY, L. 2008. Hartwell's yeast: A model organism for studying somatic mutations and cancer. Nature Education, 1, 183.

ZEEVI, D., LUBLINER, S., LOTAN-POMPAN, M., HODIS, E., VESTERMAN, R., WEINBERGER, A. & SEGAL, E. 2014. Molecular dissection of the genetic mechanisms that underlie expression conservation in orthologous yeast ribosomal promoters. Genome Research, gr.179259.114.

BASSET, D, E. & HIETER, M, S. 1996. Yeast genes and human disease. Nature, 379, 589

PEARCE, D, A. & SHERMAN, F. 1998. A yeast model for the study of Batten disease. Genetics, 95, 4.





The function of genes and subsequent proteins in yeast will continue to be mined
orthologs
noncoding RNAs
small proteins (<100 amino acids)

Role in pharmaceutical areas


By Josephine, Tu and Sofia
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