The many faces of yeast

Stefan Hohmann Department of Cell and Molecular Biology stefan.hohmann@gu.se

What is yeast/???
Yeast is a fungus, related to molds The entire organism is only one single cell Belongs to the group of ascomycetes Proliferates by budding (therefore budding yeast) Cell division results in a mother cell and a daughter cell

Where does yeast live???

Actually, we do not really know so well... But fruits and flowers are the places where yeast is very common

How does yeast get from one place to another???

It uses insects, such as the fruitfly Drosophila as vehicle

What does yeast do???

Yeast converts sugars to ethanol and carbon dioxide in alcoholic fermentation (glycolysis)

What is yeast used for???

Wine Beer Spirits Bread Bio-ethanol Proteins Research

Is yeast an allround organism???

Specialised strains (races) for different purposes (a baking yeast wont be good for wine making)

How big and how many???

A yeast cell is about 5-7 micrometer long (i.e. 1,000 cells in a row is 5mm) In one milliliter there may be 100 million (108) yeast cells This means in a 100,000 litre fermenter there may be as many as 1016 yeast cells (100 trillion)

Yeast has sex

Yeast is small, but it is not a bacterium Yeast is a eukaryote the cell is sub-divided into organelles (nucleus, mitochondria....) Eukaryotes: fungi, plants, animals And they all have sex in order to generate new combinations of genetic material

Yeast is a model organism

Human has only about 4-5 times as many genes as yeast The basic machinery (and many genes) are similar in yeast and human It is easier to study yeast than human model organism Human nerve cell 25,000 genes Yeast cell 6,000 genes

Yeast in the laboratory

Yeast research started in the 1940ies in the Carlsberg Laboratory There are about 1,000 laboratories studying yeast in the world In 2003 the International Conference on Yeast Genetics and Molecular Biology was held in Gteborg: 1,100 participants In no other cell we know so many details up to now: we know a function to about 5,000 of the 6,000 yeast genes (why not for all genes? probably because we can not reproduce nature in the lab)

Nobel yeast
Nobel Prize in Medicine in 2001 to Leland Hartwell, Tim Hunt and Paul Nurse for their discoveries of "key regulators of the cell cycle". Using budding yeast Leeland Hartwell discovered in the early 1970ies that the different steps during cell division are controlled by specific regulatory proteins Important implications for the understanding of cancer incorrect regulation regulation of cell division

Yeast ageing
Yeast cell division results in two cells that can be distinguished mother and daughter The number of daughters a mother can produce is limited to about 25 then she dies Life span is determined by some of the same genes that determine life span in human (e.g. Werners syndrome)

Yeast age 1

Yeast diabetes
Very similar molecules/pathways control the energy balance and hence the accummulation of storage material (fat) in yeast and human Studies in yeast can therefore help to find therapies for type II diabetes and the metabolic syndrome life style diseases linked to inappropriate nutrition

Yeast stress
Very similar molecules/pathways control stress responses in yeast and human cells Studies in yeast can help to understand - for instance how cells control their water household

Systems Biology: yeast in the computer

The interactions, reactions, all we know about a process is decoded in mathematical equations Computers run simulations of the process If the simulations are different from the experimental results in the laboratory we lack knowledge and then can do further studies to fill this gap Mathematical models will help to design new therapies for many diseases
Phosphorelay module
high osmolarity v2TCS ? v1TCS Sln1HisP Sln1 Sln1AspP
ADP ATP

Osmotic stress
Sln1 Plasma membrane
Internal osmotic pressure

v3TCS Ypd1 v4 Ypd1HisP

TCS

Signal pathway

Phospho relay Ssk1 system

External osmotic pressure synthesis v10

v1

Glucose uptake
ATP ADP

Glucose Glk1 v2 Gluc-6-P v3

ATP ADP

Metabolism module

Glycerol, ex v13 Fps1 Glycerol Gpd1 v11

NADH NAD

Ssk1AspP Ssk1 v5TCS Pi

MAP kinase Hog1 cascade cytosol Hog1 nucleus

Transcription

Glucose DHAP
Gpd1

ADP ATP

Fruc-1,6-BP

Metabolism
G3P
Gpp2
NAD 2 ADP 2 ATP NADH

v4 GAP v6 v5 DHAP

v12 Gpp2 G3P

Ssk1 v1MAP Ssk2

Pi ATP ADP

Ssk2P

MAP kinase cascade module

Glycerol GPD1, GPP2,.

Translation

ATP ADP

Gpd1, Gpp2,.

Fps1

Gene expression
v3MAP
ATP ADP

Glycerol extern

Pyruvate
4 NAD 4 NADH

v9

synthesis
NADH NAD

NADH

v16 v14

NAD

v-1MAP v2MAP
ATP ADP

v7 v8 3 CO2

Pbs2P

Osmotic stress
Hog1P2 vtrans cytosol v5MAP nucleus Hog1P2nuc Hog1 vtrans1 vtrans2 vpd vtl Proteins vrd

Ethanol

ADP

v15

ATP

Pbs2 v-2MAP
Pi

Pbs2P2 v-3MAP

Pi

v4MAP
ATP ADP

Hog1P

Gene expression module

Biophysical changes i = f(Glycerol) Waterflow over membrane = f(i, e, t) Volume change = f(Waterflow)
(see text)

ATP ADP

Hog1 v-4MAP
Pi

Hog1P2 v-5MAP

Ptp2 Hog1nuc vdephos mRNAnuc vex

Pi

vts

mRNAcyt

Is there a Yeast future???

Every day trillions and trillions of yeast daughters are born all over the planet Every day billions of people eat bread and drink wine and beer Every day thousands of researchers experiment with yeast and break new grounds in molecular cell biology and systems biology Questions?