Model Organisms: Saccharomyces cerevisiae by Nairita Maitra

Scientists have always sought a living organism that can simplify our understanding of a complicated system, e.g., the human body. What if I tell you that there exists a unicellular cell, easy to study, can be genetically engineered (adding or deleting specific genes from the organism), also did, I mention, it has a strong resemblance to the human genome? That’s what my model organism is: Saccharomyces cerevisiae, popularly known as baker’s yeast or brewer’s yeast. It has earned its name from ‘Sccharon’ means sugar, and ‘myces’ means fungus. Next time when you are baking a bread, you can appreciate that the yeast behind the fluffiness of your bread can encode information as much as a normal human being can.

Fig.1 Main features of a typical S. cerevisae.
Saccharomyces cerevisiae in the production
of fermented beverages: Graeme M Walker and
Graham G Stewart Beverages 2016, 2(4), 30.

Saccharomyces cerevisiae or budding yeast is a small unicellular eukaryotic organism. It is round to ovoid with a  size ranging from 5-10μm (1/1000^th of a rain droplet!!!). It optimally grows at a temperature of 30^◦C and survives on simple carbohydrates, such as glucose, fructose, glycerol, etc. In the presence of oxygen, the yeasts degrade the glucose into smaller metabolites, eventually harnessing the energy, ATP. However, under low availability of the oxygen, they ferment glucose into ethanol and carbon dioxide, and this is the CO₂ that gets trapped inside the flour dough and helps it to rise.

Unlike bacteria, budding yeasts have their nucleus encircled by a membrane (nuclear envelope) and constitute organelles (mitochondria, endoplasmic reticulum, etc., Fig 1) designed to carry out specific functions (respiration, protein synthesis, etc.).  A single cell of budding yeast is invisible to our eyes. Once they have reproduced enough and formed colonies of cells, they can be visible growing either in a liquid media or on a gel-like solid media (agar, or even on cheese or grapes). The light microscope comes in aid when one needs to take a glimpse of the cells.

Budding yeasts check off most of the eligibility criteria to serve as an ideal model

Fig.2 Cell cycle stages of S. cerevisiae. The Cell:
A molecular approach (3rd Ed) Fig 14.5

organism. They are small, non-pathogenic, easy to grow (the doubling time of yeast is just 90mins!!) and hence can be cultured and maintained at a lower expense. Budding yeast was the first eukaryotic genome to be fully sequenced and became instrumental in assigning functions to many previously uncharacterized genes. Easy addition or deletion of genes within the organism makes it more intriguing to study and model regulatory pathways of genes in yeasts. Although it may seem that yeasts and humans have very little in common, however, being a eukaryote, yeasts share the similar internal complicated cellular system as the human cells. More than half of the protein-coding genes within yeast are found to have homologs in human cells. Hence, translating yeast research into human research is becoming more and more feasible.

Since the 1990s, S. cerevisiae has been instrumental in the studies of the cell cycle, and the extensive work has also been rewarded in early 2000 by the Nobel Prize to Lee Hartwell, Paul Nurse, and Tim Hunt. They discovered the cell division cycle (CDC) genes that play a significant role in regulating the transition into different phases of the cell cycle(G1, S, G2, and M phases Fig 2). The cellular mechanism of the cell cycle is highly conserved from yeasts to higher eukaryotes like human cells. The Cell cycle begins with the cells growing; eventually, they pass through several checkpoints (Nutrient availability etc.) before they ‘START’ (the restriction point in human cells) at least one round of DNA replication and finally divide into the daughter cell. Along with different organelles, the nucleus also undergoes doubling, and at the end of each cell cycle, every cellular component is evenly distributed into the daughter cell.

Fig.3 The nuclear division in budding yeast.
Sizing up the nucleus: nuclear shape, size and nuclear-
envelope assembly: Micah Webster, Keren L. Witkin, Orna Cohen-Fix
Journal of Cell Science 2009 122: 1477-1486;
doi: 10.1242/jcs.037333

Cells are expected to grow to a specific size before they can undergo division. They maintain a tight balance between growth and division to ensure that with each generation, cells do not become progressively larger or smaller. A critical requirement to achieve the balance between cell growth and division is the regulated synthesis of proteins and lipids during every cell cycle. Bulk protein synthesis is necessary to maintain the cell’s mass, and fats are required for cellular membrane synthesis. My study states that genes encoding for lipid synthesis are regulated in the cell cycle. It is of no surprise that the demand for lipids increases to serve the need for the synthesis of new organelles for the new budding daughter cell. However, in my study, I succeeded in establishing a unique role to the lipid genes. We show that when lipid genes are in abundance, especially during the late phases of the cell cycle(G2 and M), they accelerate the nuclear division(Fig 3). We propose that nuclear division serves as the cue for coordination between cell division and growth.

Budding yeast is the most compatible model organism to study cell cycle. Every phase of the cell cycle can be precisely monitored with the formation of buds. The size of the bud and the ratio of the bud size and the mother size can determine the phase within the cell cycle accurately. Nonetheless, due to the similar eukaryotic behaviour, genes found to control cell division in yeasts perform identical functions in human cells as well. With the discovery of more such genes that serve as either the accelerator or brake in the cell cycle and division, we will be able to eventually uncover the molecular mechanism behind the uncontrolled growth and division of a cancer cell and other proliferative diseases. In fact,  the lipid genes, such as FASN, behave as an accelerator in the cell cycle (nuclear division accelerator in my study) are under clinical trial for the therapeutic target for cancer.

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Nairita Maitra

Email: nairitamaitra@tamu.edu

Twitter : @maitra_nairita

Lab: The Polymenis Lab, Dept. Of biochemistry and Biophysics, Texas A&M University