'How do we know what we don't know?': Scientists completely define the process of methylation

The crucial cellular process known as methylation has now been fully characterized by UNSW Sydney researchers for the first time. The groundbreaking discovery highlights the critical part methylation plays in the production of proteins in an article that was published in the Proceedings of the National Academy of Sciences.

Methylation is a chemical process in which a methyl group, a tiny molecule, is added to, or "tagged," onto, DNA, proteins, or other molecules. Methylation, for instance, can influence a cell's behavior by promoting stem cell growth and differentiation.

The School of BABS's Dr. Joshua Hamey and Professor Marc Wilkins have jointly specified in detail which proteins in yeast cells bear methyl groups, where the tag is located, and what machinery has been employed to get them there.

According to Dr. Hamey, the study's principal author, "some aspects of the cell have been thoroughly understood for a while, such as the DNA sequence of many genomes." Other processes, like the chemical protein tagging that occurs in cells, are, on the other hand, seldom ever thoroughly understood.

"We've used a formal method to find out exactly what we don't know about methylation," claims Dr. Hamey. The two have concluded that after carefully examining all of the methylation-related literature, there is actually very little more that needs to be learned about this process.

Dr. Hamey claims, "We've provided a nearly full description of this system. It also raises intriguing new concerns about the system as a whole and what this methylation tag truly does, even if it seems that there isn't any more information to be learned in this area.

Is there ever anything new to learn?

According to Prof. Wilkins, "Our work focuses on attempting to understand how cells manage information and make decisions." This is significant because cells constantly choose whether to continue growing or stop in order to respond to environmental changes.

In a cell, proteins may be marked with tiny molecules that act as units of information or data, which is something that has long been recognized. However, up until now, we were unable to determine the precise number of protein tags present in every given cell as well as the mechanism used to attach them.

The methylation system consists of enzymes that alter another protein by 'tagging' it with a tiny molecule, in this instance a methyl group. A person's risk of contracting certain diseases, including cancer, can be influenced by changes to the methylation patterns of genes or proteins as well as by the addition of methyl groups, which can alter how some molecules behave in the body.

According to Prof. Wilkins, "We have been conducting experiments in this area for a very long time." Using yeast as a model organism for human and animal cells, I set out to describe this specific sort of cell alteration (methylation).

Prof. Wilkins, Dr. Hamey, and other researchers in the area uncovered more aspects of this process over time, to the point where less and fewer aspects were being found.

The more we looked, the less we really discovered, according to Dr. Hamey. There is always more to learn, according to the current paradigm in this discipline. This research, however, challenges that notion.

defining the methylation system

Dr. Hamey and Prof. Wilkins collectively conducted a comprehensive review of all the literature that has been written about the methylation process in yeast. According to Prof. Wilkins, "We developed a method to categorize the evidence for and against there being "more" to learn about the biological system of methylation.

The central component of this system, the protein that is being methylated, and the enzyme that carries the methyl group are connected in any methylation process. Dr. Hamey explains that if there is more to learn, there will likely be a relationship between these two proteins that we are unaware of.

"We were able to use the knowledge of this connection to catalogue the existing evidence and determine whether there are more of these connections that remain unknown—and if so, how many."

They got to the conclusion that methylation in the model organism yeast is almost fully known as a result of this methodical research.

Controlling cell behavior and development

Numerous of these methylation events have critical roles in both regulating the cell's responsiveness to external inputs and internal signaling. The machinery that creates proteins within the cell, in particular, is controlled by these signaling pathways.

"As a result of our systematic review, we can say that this system seems to be mostly about controlling the way that the cell makes proteins, which is central to how the cell functions," claims Dr. Hamey.

A thorough understanding of methylation and its crucial function in protein synthesis throws up new possibilities for how we might be able to regulate some elements of cell development and behavior.

The results have immediate implications for the manipulation of yeast in activities like brewing, baking, and biofuels as well as how yeast and fungal infections in patients—such as candidiasis and tinea—can potentially be treated, according to Prof. Wilkins. "We focused our work on the yeast cell—which has many similarities to the human cell but is simpler to study," he adds.

Furthermore, with this comprehensive map in hand, Dr. Hamey adds, "we are now able to pose systematic questions about why this system originated and its role in regulating essential biological processes. "These are the issues we are currently dealing with."