New mathematical model reveals how yeast decide whether to mate - <em>News Release</em>

Imperial College London News Release

Under strict embargo until:
1800 BST / 1300 ET
Sunday 18 April 2010

Yeast cells decide whether to have sex with each other within two minutes of meeting, according to new research published today in Nature. One of the authors of the study, from Imperial College London, says the new insights into how yeast cells decide to mate could be helpful for researchers looking at how cancer cells and stem cells develop.

Yeasts are single-celled microbes that scientists often use as model organisms, to help them understand how cells work. They usually reproduce asexually, by a process called budding, where a part of the cell is pinched off and becomes a new cell, identical to the original.

Sometimes, yeast cells reproduce sexually, by mating. The mating process involves one cell of each sex joining together, then mixing their DNA and splitting apart again. To do this, the cells each have to produce a nodule that they can join together, called a shmoo. The process of shmooing takes around two hours.

In today's new study, researchers from Imperial College London, Université de Montréal, McGill University and the University of Edinburgh determined that a yeast cell's decision to mate is controlled by a chemical change on a single protein. This change occurs two minutes after the cell detects a pheromone produced by the opposite sex, meaning that the decision to mate occurs much more quickly than scientists previously thought.

The researchers also found that in order for the mating process to be switched on, the pheromone must reach a critical concentration in the environment around the yeast cell. Below this concentration, the yeast cell continues to reproduce asexually.

"Shmooing is a very energy-intensive process for yeast cells. We think this switching process at a certain pheromone concentration may have evolved to make sure the cells only get prepared for sexual reproduction if a mate is sufficiently close enough and able to mate," said Dr Vahid Shahrezaei, one of the authors of the study from the Department of Mathematics at Imperial College London.

Dr Vahid Shahrezaei illustrates his findings

The researchers used a highly complex mathematical model to determine what switches the mating process on and off, factoring in experimental data about the concentration of pheromones around the cell, the concentrations of different proteins relevant to mating inside the cell and how strongly these proteins bind together.

They believe their mathematical model can potentially be used to investigate the triggers that cause changes in other cells, such as stem cells becoming heart or bone cells, or normal cells becoming cancerous. This is because mammalian cells and yeast cells contain many of the same proteins, which work together in a chain reaction to trigger a decision in the cell. Therefore, today's new model could ultimately help researchers to develop new drugs and therapies.

Dr Shahrezaei said: "Yeast cells live in a very noisy environment - they are surrounded by different chemicals, including pheromones and food, and their own machinery inside the cell produces lots of biomolecules that interact with each other. We wanted to see how cells make sense of this noisy environment and work out what is happening, at a molecular level, to make a important decision like mating.

"By combining experiments and mathematical modelling that take lots of different factors into consideration, we have been able to show exactly what is happening inside a yeast cell to make it decide whether to mate with another cell. We also showed that the mechanism that leads the cells to make their decision is very robust, meaning it is not affected by molecular noise in the environment," added Dr Shahrezaei.

"Although yeast is dramatically different from people, at a molecular and cellular level we have a lot in common," said senior author Dr Stephen Michnick, a Université de Montréal biochemistry professor and Canada Research Chair in Integrative Genomics. "The same molecules that create the switching decision in yeast are found in very similar forms in human cells. Similar switching decisions to those made by yeast are made by stem cells during embryonic development and become dysfunctional in cancers."

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Notes to Editors:

1. "The scaffold protein Ste5 directly controls a switch-like mating decision in yeast" Nature, 18 April 2010. Dr Vahid Shahrezaei, Imperial College London (For a full list of authors, please see paper)

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality.

Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy.

Website: www.imperial.ac.uk

3. About McGill University

McGill University, founded in Montreal, Que., in 1821, is Canada's leading post- secondary institution. It has two campuses, 11 faculties, 10 professional schools, 300 programs of study and more than 35,000 students. McGill attracts students from more than 150 countries around the world. Almost half of McGill students claim a first language other than English - including 6,200 francophones - with more than 6,800 international students making up almo st 20 per cent of the student body.