Epigenetics Explained

We caught up with Sebastian Scheer, who researches epigenetics in the immune system at Monash University in Melbourne, Australia with the Zaph Lab. And what exactly is epigenetics? We weren’t sure either. But Sebastian broke it down for us.

While geneticists look at changes in DNA sequences, epigeneticists don’t focus on the DNA sequence itself but rather on the modifications of the DNA and the proteins that DNA is wrapped around, called histones. Histone tails can be altered by enzymes called epigenetic modifiers, and these modifications change the “readability” of a person’s DNA. As a result each cell has a unique epigenetic landscape.

Did you follow that? A real world example helps bring this concept home. Identical twins have the same exact DNA, but as humans they present slight differences. Epigenetics (as well as a host of other factors) contribute to these differences. While identical twins have the same DNA, their cells may show different epigenetic landscapes. Epigenetics play a part in many functions of the human body including immune system responses.

Sebastian (left) at the Zaph Lab.

Experimentation

Sebastian investigates how epigenetics shape T cells, the central cells of the immune system. When a pathogen enters the body, T cells direct the immune response based on what that pathogen is. For example, a viral infection will trigger a so-called ‘Th1 immune response’, while asthma will trigger a ‘Th2 immune response’.

So how exactly do T cells, immune responses and epigenetics all relate? The Zaph Lab has various genetic models available that allow them to analyze how epigenetic modifiers influence the characteristics of T cells. The characteristics of T cells influence how they direct immune responses. In short, the Zaph Lab looks at how different epigenetic modifiers either amplify or mitigate T cells’ effectiveness at directing immune system responses.

The lab has found that when epigenetic modifier G9a is inhibited, more regulatory T cells develop. Regulatory T cells help treat intestinal inflammation. That being said, G9a might be a candidate for further investigation as less G9a means more regulatory T cells to attack and resolve that inflammation.

Understanding how we can manipulate epigenetic modifiers to improve immune system responses has huge potential implications for the medical field. If we can boost T cells’ effectiveness by providing them with, or depriving them of, the right epigenetic modifiers at the right time, we can better direct immune responses leading to faster healing times and better health outcomes overall.

Recording Data

The Zaph Lab is conducting research that is highly detailed and requires quite a bit of data collection. How they collect, record and preserve that data bears significantly on the efficacy of their research both now and down the track. Sebastian starts work at the lab each day by opening LabArchives which he uses as “a regular lab notebook.” Sebastian and the seven other researchers in Professor Colby Zaph’s laboratory all use LabArchives to record their data.

These researchers put every experiment into LabArchives so that all lab members have access to it. This allows them to keep track of data when someone leaves the lab and ensures that no data is lost over time. This is hugely important for the lab as they go to publish their findings (more on this in a bit).

Sebastian, like many researchers, started out with a paper notebook system. When he moved from Vancouver to Monash in 2015, Professor Zaph and Sebastian were approached by a Monash team tasked with finding a digital notebook solution. Now safely on the digital side of things, Sebastian looks back on hard copy days without remorse, “Nope I don’t ever miss using paper. I always ended up recording my data digitally anyways, this is so much more convenient.”

Zaph Lab Setup

LabArchives is a central point of reference for the entire Zaph Lab. The lab’s eight researchers all have access to the right information at the right time via LabArchives. An accessible folder holds the lab’s protocols, standards operating procedures (SOPs), experimental data, recipes and an inventory for the lab.

As soon as an experiment is completed the researchers add a new page to the experimental data folder, give it a specific experimental number and label the test tubes used with that number. With this system the lab can refer back to LabArchives, see how an experiment turned out and locate which test tubes were used in that experiment.

The Zaph Lab also works with PRISM to visualize their data. Sebastian often “save(s) files in PRISM, transfer(s) them directly to LabArchives and then move(s) the files from the LabArchives inbox to the experiment.” So convenient.

And where has all this work led the Zaph Lab?

Since Sebastian started at Monash the Zaph Lab has successfully published four scientific papers. The lab most recently published an article in Nature Communications.

In this paper, the Zaph Lab mimicked T cells’ development from naïve T cells to effector T cells. This normally occurs after a flu infection (the infection prompts T cells to develop and respond). To analyze the effect of epigenetic modifiers on T cell development, the lab incubated T cells with a drug that inhibits epigenetic modifiers. The lab was then able to analyze the impact of epigenetic modifiers on the development of T cells and their ability to direct an immune response to the flu infection.

During this screening process, the lab found a key epigenetic modifier that dampens the pro-inflammatory qualities of T cells. Once this epigenetic modifier was found, the lab began to organize their data for publication.

The Zaph lab looks at how epigenetic modifiers influence T cell’s ability to direct effective immune responses.

Preparing data for publication can be a total headache. Especially if your lab has to comb through heaps of messy paper notebooks to do this. But as Sebastian mentioned, “LabArchives makes it so easy to assemble data for publication since we have all our data stored in one place, just one click away. As you can imagine this screening process produced a lot of data and the paper was quite complex.”

All of this important data lives in LabArchives. It is safely stored, accessible only to the right people and is always there to back up the Zaph Lab’s findings. The lab is already following their most recent discovery up with further experiments to better understand the implications of this epigenetic modifier, and Sebastian is hard at work writing up the lab’s next paper!