epigenetics

Seminal work

How unruly data led MU scientists to discover a new microbiome
By Roger Meissen | MU Bond Life Sciences Center

seminal vesicles 3_11_16.jpg

This seminal vesicle contains a newly-discovered microbiome in mice. Some of its bacteria, like P. acnes, could lead to higher occurrences of prostate cancer. | contributed by Cheryl Rosenfeld

It’s a strange place to call home, but seminal fluid offers the perfect environment for particular types of bacteria.

Researchers at MU’s Bond Life Sciences Center recently identified new bacteria that thrive here.

Cheryl Rosenfeld1.jpg “It’s a new microbiome that hasn’t been looked at before,” said Cheryl Rosenfeld, a Bond LSC investigator and corresponding author on the study. “Resident bacteria can help us or be harmful, but one we found called P. acnes is a very important from the standpoint of men. It can cause chronic prostatitis that results in prostate cancer. We’re speculating that the seminal vesicles could be a reservoir for this bacteria and when it spreads it can cause disease.”

Experiments published in Scientific Reportsa journal published by Nature — indicate these bacteria may start disease leading to prostate cancer in mice and could pass from father to offspring.


A place to call home

From the gut to the skin and everywhere in between, bacterial colonies can both help and hurt the animals or humans they live in.

Seminal fluid offers an attractive microbiome — a niche environment where specific bacteria flourish and impact their hosts. Not only is this component of semen chockfull of sugars that bacteria eat, it offers a warm, protected atmosphere.

“Imagine a pond where bacteria live — it’s wet it’s warm and there’s food there — that’s what this is, except it’s inside your body,” said Rosenfeld. “Depending on where they live, these bacteria can influence our cells, produce hormones that replicate our own hormones, but can also consume our sugars and metabolize them or even cause disease.”

Rosenfeld’s team wasn’t trying to find the perfect vacation spot for a family of bacteria. They initially wanted to know what bacteria in seminal fluid might mean for offspring of the mice they studied.

“We were looking at the epigenetic effects — the impact the father has on the offspring’s disease risk — but what we saw in the data led us to focus more on the effects this bacterium, P. acnes, has on the male itself,” Rosenfeld said. “We were thinking more about effect on offspring and female reproduction — we weren’t even considering the effect the bacteria that live in this fluid could have on the male — but this could be one of the more fascinating findings.”

But, how do you figure out what might live in this unique ecosystem and whether it’s harmful?

First, her team found a way to extract seminal fluid without contamination from potential bacteria in the urinary tract.

“We gowned up just like for surgery and we had to extract the fluid directly from the seminal vesicles to avoid contamination,” said Angela Javurek, primary author on the study and recent MU graduate. “You only have a certain amount of time to collect the fluid because it hardens like glue.”

Once they obtained these samples, they turned to a DNA approach, sequencing it using MU’s DNA Core.

They compared it to bacteria in fecal samples of the same mice to see if bacteria in seminal fluid were unique. They also compared samples from normal mice and ones where estrogen receptor genes were removed.


The difference in the data

It sounds daunting to sort and compare millions of DNA sequences, right? But, the right approach can make all the difference.

“A lot of it looks pretty boring, but bioinformatics allow us to decipher large amounts of data that can otherwise be almost incomprehensible,” said Scott Givan, the associate director of the Informatics Research Core Facility (IRCF) that specializes in complicated analysis of data. “Here we compared seminal fluid bacterial DNA samples to publicly available databases that come from other large experiments and found a few sequences that no one else has discovered or at least characterized, so we’re in completely new territory.”

The seminal microbiome continued to stand out when compared to mouse poop, revealing 593 unique bacteria.

One of the most important was P. acnes, a bacteria known to cause chronic prostatitis that can lead to prostate cancer in man and mouse. It was abundant in the seminal fluid, and even more so when estrogen receptor genes were present.

“We’re essentially doing a lot of counting, especially across treatments to see if particular bacteria species are more common than others,” said Bill Spollen, a lead bioinformatics analyst at the IRCF. “The premise is that the more abundant a species is, the more often we’ll see its DNA sequence and we can start making some inferences to how it could be influencing its environment.”

Although this discovery excites Rosenfeld, much is unknown about how this new microbiome might affect males and their offspring.

“We do have this bacteria that can affect the male mouse’s health, that of his partner and his offspring,” Rosenfeld said. “But we’ve been studying microbiology for a long time and we still find bacteria within our own bodies that nobody has seen before. That blows my mind.”

The study, “Discovery of a Novel Seminal Fluid Microbiome and Influence of Estrogen Receptor Alpha Genetic Status,” recently was published in Scientific Reports, a journal published by Nature.

 

Oliver Rando researches effect of fathers’ lifestyles on their children

How much does a newborn know about the world?

That can depend on their parents’ genes, according Oliver Rando, an epigeneticist at the University of Massachusetts.

Rando will speak Saturday, March 14, at 10:30 a.m. at the 11th Annual Life Sciences and Society Program at Bond LSC. His research focuses on how fathers’ lifestyles affect their children, one part of the symposium’s focus on epigenetics. Epigenetics is the study of how organisms change because of a modification in gene expression.

Rando is clear that his research is no more important than that of other scientists in his field.

“The field we work in is important since we and others have shown that a father’s lifestyle can potentially affect disease risk and other aspects of his children,” he said.

During his talk on Saturday, Rando will discuss a “paternal effect paradigm” based on experiments his lab conducted on male mice. The mice were fed different diets and mated with control females. Then researchers analyzed the metabolic effects that resulted in their offspring.

“In terms of the basic science aspects of the system, doing this sort of experiment with fathers rather than mothers is important, since mothers provide both an egg and a uterus to the child, whereas in many cases fathers only provide sperm,” Rando said. “So, with fathers you don’t have as many things to look at to find where the relevant information is.”

Scientists in his lab also study yeast and worms to understand epigenetic inheritance. They use molecular biology, genetic and genome-wide techniques to conduct the research.

For more information about Dr. Oliver Rando, read this Q&A from the Boston Globe.

Find more information about LSSP events and speakers at http://lssp.missouri.edu/epigenetics.

Five things you wanted to know about epigenetics (But were afraid to ask)

10960203_781430608590258_4910408420147962125_oWhat the heck is it, anyway?

Epigenetics involves changes in how your genes work.

In classical genetics, traits pass from generation to generation in DNA, the strands of genetic material that encode your genes. Scientists thought alterations to the DNA itself was the only way changes could pass on to subsequent generations.

So say you lost a thumb to a angry snapping turtle: Because your DNA hasn’t changed, your children won’t be born with smaller thumbs. Classic.

Things get way more complicated with epigenetics. It turns out that some inherited changes pass on even though they are not caused by direct changes to your DNA. When cells divide, epigenetic changes can show up in the new cells.

Getting nibbled on by an irate turtle isn’t likely to epigenetic changes, but other factors such as exposure to chemicals and an unhealthy diet, could cause generation-spanning epigenetic changes.

 

How does it work?

The main players in epigenetics are histones and methyl groups.

Imagine your genes are like pages in a really long book. Prior to the mid-1800s, books came with uncut edges, so in order to read the book, you’d have to slice apart the uncut pages. That’s sort of what a histone does to DNA: They are proteins that wrap DNA around themselves like thread on a spool. They keep the DNA organized and help regulate genes.

Methyl groups (variations on CH3) attach to the histones and tell them what to do. These molecules are like notes in a book’s margin that say, “These next few pages are boring, so don’t bother cutting them open.” As you read the book, you’ll save time and effort by skipping some sections even though those sections still exist. Or maybe the note will say, “This next section is awesome; you’ll want to read it twice.”

That’s epigenetics. Higher level cues that tell you whether or not to read a gene.

And when a scribe makes a copy of the book, they’ll not only copy all the words in the novel, but all the other stuff, too: the stuck-together pages and the margin notes.

 

What about my health?

Many areas of health — including cancer, autoimmune disease, mental illness and diabetes — connect with epigenetic change.

For example, scientists link epigenetic changes to neurons to depression, drug addiction and schizophrenia. And environmental toxins — such as some metals and pesticides — can cause multigenerational epigenetic effects, according to research. Once scientists and doctors decipher those processes work, they will be better equipped to treat the sick and be able to take preventative measures to help insure our health and the health of our kids.

 

Is it epigenetics or epigenomics?

Confusing, I know.

As we learned from the first question, epigenetics is “the study of heritable changes in gene function that do not involve changes in the DNA sequence,” according to my trusty Merriam-Webster.

Epigenomics is the study and analysis of such changes to many genes in a whole cell or organism. It’s comparable to the difference between genetics (dealing with particular pieces of DNA, usually a gene) and genomics (involving the whole genetic shebang).

 

Where can I learn more?

Start at this year’s Life Sciences and Society Program Symposium, “The Epigenetics Revolution: Nature, Nurture and What Lies Ahead,” on March 13-15, 2015. Speakers from all over the country will delve into the puzzles and possibilities of epigenetics.

For more background, Nature magazine also created this supplement on epigenetics.