Scientist Thomas Braun speaks at Bond LSC about skeletal muscle regeneration. Braun is the director of the Max-Planck Institute that studies the heart,lungs and blood vessels.| Photo by Samantha Kummerer, Bond LSC
By Samantha Kummerer | Bond LSC
Thomas Braun, a researcher with the German-based Max Planck Institute for Heart and Lung Research, visited MU for a Bond Life Sciences and Mizzou Advantage seminar.
The Max Planck Institute aims to find treatment for heart and lung disease. Part of its research focuses on stem cells and how they can decrease damage done to patients’ tissues who suffer from heart or lung disease.
Many components can interfere with effective muscle regeneration and a lot of those this components are connected to cell death.
Braun’s talk focused on the epigenetic and transcriptional control involved in skeletal muscle regeneration. His research explores cell death’s effect on muscle regeneration. They initially hypothesized that cell death would interfere with regeneration.
Muscle regeneration requires satellite cells. Satellite cells, aptly named for being located near muscle and nerve cells, help skeletal muscle fibers grow, repair and regenerate.
When cells become obsolete they activate a cell program to commit suicide. This cell death comes in the form of apoptosis — normal programmed cell death triggered to eliminate old, unnecessary or unhealthy cells — and necroptosis that is a death by inflammation to counter viruses and other disease.
Braun said when muscle fibers break down there is lots of killing of cells.
“We wanted to see if we take the muscle stem cells out of the tissue and put them into a dish whether they would still maintain this increased function to undergo program cell death and quite interestingly this enhanced tendency to go into cell death is actually maintained even after a few different transitions in vitro,” Braun said describing a particular experiment.
This increase cell death, Braun hypothesized, is caused by changes in the chromatin, a complex of DNA and protein.
To better understand exactly which cell death program was responsible for this increase, Braun’s team repeated the experiment but block certain components. This led them to discover the increased cell death correlates with an increase in necrosis.
Braun also believes there are some epigenetic mechanisms involved. Epigenetic involves biological mechanisms that switch genes on and off.
CDH4 is a component of a complex within this epigenetic function. The larger complex is a repressor and keeps the chromatin together. The researchers thought CHD4 might be what is acting on the pathways
“This actually goes along with a massive increase in cell death so this lack of proliferation of the fiber is simply dependent or caused by the cell death of these satellite cells. They undergo cell death and therefore cannot proliferate,” Braun explained.
Braun said his team landed on the conclusion that normally CDH4 represses the expression of
RIBK3, a protein-coding gene, and thus prevents necrosis cell death. But without CHH4, necrosis begins, cells die.
There are still many questions and experiments that lie ahead to figure out the details involved.
Braun’s talk was made possible by the support of Mizzou Advantage and Bond LSC.
How unruly data led MU scientists to discover a new microbiome By Roger Meissen | MU Bond Life Sciences Center
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.
“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 Reports — a 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 Genomics Technology 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.”
Joya Chandra, associate professor of pediatrics at The University of Texas MD Anderson Cancer Center, explains the epigenetics of pediatric cancers at the 2015 MU LSSP Symposium on epigenetics on Sunday, March 15.//photo by Caleb O’Brien/Bond LSC
The evolving science of epigenetics is shaking up how scientists and doctors think about cancer.
At the 11th annual University of Missouri Life Sciences & Society Program symposium, scientists, historians and philosophers explored the epigenetic theme. On its final day, two researchers spoke about how cancer and epigenetics intersect.
Epigenetics involves changes to how genes work that do not occur within DNA. Epigenetic changes can, in effect, turn genes on or off, and those changes can then be passed from generation to generation. Because cancer involves cells that grow uncontrollably, don’t die and can travel throughout the body, it makes sense to look for epigenetic changes that could account for cancer’s unusual attributes.
Shuk-mei Ho, director of the University of Cincinnati Cancer Center and Chair of the Department of Environmental Health, discussed the developmental origins of health and disease (DOHaD) hypothesis, which suggests that problems early in development or during other key periods such as puberty and pregnancy can have wide-ranging implications later in life.
She centered on whether early exposure to a high fat diet and endocrine disruptors such as bisphenol A can affect an offspring’s risk of developing certain types of cancer.
“These studies are really important because they help us identify some early warning signs that may be related to epigenetics,” she said “They allow us to devise measures that we can use to interfere with and prevent development of cancer.”
A proactive approach to cancer could harness science’s newfound understanding of epigenetics and target cancers before they start.
“It is much more effective to have prevention rather than have the cancer and devise ways to treat it,” she said. “This will minimize a lot of suffering and also reduce the cost of the health care.”
Prevention is especially important because epigenetic effects can arise quickly and persist for multiple generations. For example, breast cancer rates in immigrant populations can increase within one generation of arrival. In mice, scientists have detected the lingering effects of a high fat diet after three generations.
Epigenetics and childhood cancer
Pediatric oncology is especially apt for integration with epigenetics.
Joya Chandra, associate professor of pediatrics at the University of Texas MD Anderson Cancer Center, studies therapies for childhood cancers. She said developments in epigenetics have helped researchers better understand childhood cancers and the ways they differ from adult cancers.
“The field of epigenetics has just exploded in terms of giving us insight into how pediatric cancers are different from adult cancers.” Chandra said. “Just in the past 2-3 years we’ve learned a lot about cancers that are present in adults and children that have really different epigenetic profiles. This presents an opportunity for pediatric cancer oncologists to treat these cancers differently, and increasing knowledge about epigenetics will help serve that goal.”
leukemia, for example, is the most common pediatric cancer but only the sixth most common among adults. And about 70 percent of infants with leukemia exhibit epigenetic changes associated with their cancer.
Children with glioblastoma, a type of brain cancer, exhibit epigenetic traces that are distinct from the same kind of cancer in adults.
A deeper understanding of epigenetics and of how cancer in children differs from adult cancer could allow for the development of new medicines, novel therapies and powerful strategies for proactively protecting patients from certain types of cancers.
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.
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.
LSSP Symposium highlights epigenetics of the womb and how parental stress can change genetic makeup
Could a stressful day during pregnancy change the future of a developing child nestled in the womb?
Experts in the epigenetic research field are saying yes.
This weekend the 11th annual Life Sciences and Society Program will kick off “Epigenetic Revolution: Nature, Nurture and What Lies Ahead,” bringing experts on environmental influences on offspring to the stage.
Two speakers will focus their talks on the period of time developing mammals spend in the womb and what factors could trigger changes in their genetics. Tracy Bale, from the University of Pennsylvania, and Irva Hertz-Picciotto., from UC Davis, promise to draw the largest crowds.
“I heard great things about Tracy Bale’s innovative research — several senior colleagues called her a rising star in the field — so we were keen to invite her,” said LSSP Symposium Director Mary Shenk. “The connection to neurodevelopmental disorders like autism was of strong interest on campus.”
Epigenetic research has could provide answers to some of our longest standing questions.
Epigeneticists reason that the nature versus nurture development notion doesn’t consider their overlap. The premise is that our future is not only influenced by the genetics of our parents, but also tweaked further down the line by environmental factors.
Don’t miss it: Stress Parents
Tracy Bale, professor of neuroscience and animal biology at the University of Pennsylvania, will present “Stress Parents: Maternal and Paternal Epigenetic Programming of the Developing Brain” in Monsanto Auditorium at 9 am on Saturday.
Tracy Bale will speak in Bond Life Sciences Center’s Monsanto Auditorium at 9 a.m. Saturday. Her talk, “Stress Parents: Maternal and paternal epigenetic programming of the developing brain,” will cover cutting-edge research at the University of Pennsylvania where she linked parental stress, infection and malnutrition to an increased risk for the childhood development of neurodevelopmental disorders, like autism and schizophrenia.
Bale’s research provides tools to better understand how parental experiences trigger changes in their future offspring’s brain, and they could play an important role in disease risk and resilience.
She tests her theories in mice, finding epigenetic marks that were changed by male mice stress experiences. She said the research could one day translate to humans.
“If we can identify epigenetic marks in mice that are important in how their offspring develop, we might be able to understand more about human lifetime exposures to things like stress and how important such marks are in germ cells,” Bale said.
The bottom line is epigenetics can do what evolution does, but much more quickly. Bale wants the audience to walk away from her talk on Saturday morning understanding the importance of germ cells and how the influence of the environment can impact future offspring.
“This field helps to explain how an organism can rapidly respond to a changing environment and pass on potentially beneficial traits to future generations without the length of time evolution would require for such fitness,” Bale said.
Don’t miss it: Epigenetics and autism
Hertz-Picciotto will turn our discussion toward the topic of Autism: Past Evidence, Current Research and future quandaries” at 2:15 p.m. Saturday.
Her research began with three clues about autism: it tended to run in families, children with rubella had a high rate of autistic symptoms and children exposed prenatally to the drug thalidomide, show symptoms, as well.
Irva Hertz-Picciotto, professor of public health sciences at the University of California — Davis, will present “Environment and Autism: Past Evidence, Current Research and Future Quandaries” at 2:15 pm on Saturday.
“This is a controversial topic, but also an important one to learn more about given how many people’s lives are touched by autism,” Shenk said. “Dr. Hertz-Picciotto’s research and outreach work are very widely respected.”
Hertz-Picciotto, an environmental epidemiologist and professor of public health sciences at UC Davis, will highlight epigenetic studies being conducted, and key gaps, persistent myths and enigmas that still need to be solved during her talk on Saturday.
Bale and Hertz-Picciotto join many other speakers as part of this year’s LSSP Epigenetic Revolution Symposium.
The symposium begins Friday, March 13, with talks and presentations extending through March 15. Affiliated events will be going on the entire weekend, extending through March 17.
To introduce our 11th Annual Life Sciences and Society Program, The Epigenetics Revolution: Nature, Nurture and What Lies Ahead that runs at the University of Missouri March 13-15, we figured it would be nice to define the term epigenetics. Spoiler: It’s amazing and it could change everything.
According to Merriam-Webster Dictionary, epigenetics is “the study of heritable changes in gene function that do not involve changes in the DNA sequence.”
Let’s break that down.
We can inherit something that changes what our genes do, but don’t actually change the code of our DNA.
So what sort of things do genes do?
It might be easier to think about it like this: Genes are like ingredients that make up a recipe which concocts a specific function. Each individual ingredient adds to the bigger picture. Say the recipe is our height. There are many, many genes involved in myself standing at 5 feet 6 inches and my sister towering over me at 5 feet 10 inches.
Though it’s not epigenetics that makes my sister taller than me, epigenetics could help help explain why identical twins exposed to different conditions over their lifetimes, may eventually produce offspring with extreme differences in height, as just one example.
Yesterday, Jack C. Schultz, director of the Christopher S. Bond Life Sciences Center, explained epigenetics to me this way:
“We are not simply the sum of the genes we have, but rather which ones are on or off,” Schultz said. “Those differences in gene activity explain why even identical twins are not totally identical.”
Mary Shenk, the director of this year’s LSSP symposium, said epigenetics is a revolutionary area of research that changes the way we think about genetic effects. Epigenetics research makes it clear that many aspects of the environment—including the social environment—can affect how genes are expressed, she said.
“We have always known that some traits—height, for instance—were strongly influenced by the environment through diet,” Shenk said. “But new research makes it clear just how many ‘genetic’ traits are subject to either environmental influences and/or other influences such as the sex of the parent a gene is inherited from.”
“This is a real game-changer in terms of how we see the world of genes, and makes notions of simple genetic determinism of complex traits increasingly unrealistic,” Shenk added.
The key to understanding epigenetics, is to consider the capabilities of the environment to “switch on or off” the expression of our genes.
Let’s reflect on something you may have (or haven’t) heard about: “Hogerwinter,” more well known as the Dutch Hunger Winter. The historic famine from the winter of 1944 to the spring of 1945, has been the focal point in some of the most infamous epigenetic research.
Investigators wanted to know if prolonged famine conditions could have an effect on the offspring of pregnant mothers during that time.
“The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance,” by Nessa Carey published by Columbia University Press in 2012, makes a compelling argument about the famine effect on gene expression in subsequent generations.
The research looked at children who were in the second trimester of their mother’s pregnancy during the winter of 1944-1945, and they found an increased incidence of schizophrenia in those children.
Carey’s research suggests epigenetics could explain effects of famine, on the expression of certain genes of the offspring of mothers pregnant during that time.
Illustration by Paige Blankenbuehler/Bond Life Sciences Center
Epigenetics are the nucleus of the 11th Annual Life Sciences and Society Program held at the University of Missouri next weekend, March 13-15. The field has the potential to unlock some of our longest standing questions about who we are and why we are this way, scientists say. The event is a great opportunity to learn more about “The Epigenetics Revolution.”
Schultz says the field of epigenetics is exploding, and it’s important to us for three big reasons.
One: Epigenetics helps us understand how we – or any organism – can cope with changing conditions even though we can’t change our genetic makeup.
Two: Epigenetics explains how traits can be passed from parent to offspring without changing genetic makeup.
Three: Many human diseases, including cancer, seem to involve epigenetic activity. Experiences of the parents, or of developing embryos in the womb could be responsible for difficult-to-understand problems in the offspring, such as cognitive disorders including autism spectrum disorders.
“Discovering how epigenetics works is like discovering an entirely new language,” Schultz said. “That language links our experiences – even emotional ones – to the way we are and the way our offspring look and behave.”
Schultz said exploring those links can help us understand how our environment shapes us and our societies.
According to Shenk, director of the Life Sciences and Society Program, the nine speakers coming to the MU campus all bring their own expertise to epigenetics. As far as picking a speaker, Shenk said it’s hard to choose just one.
Nonetheless, here are a few to keep on your radar, according to Shenk:
“I am especially looking forward to hearing Annie Murphy Paul talk about her experiences writing about maternal effects for a general audience.
“Tracy Bale and Oliver Rando discuss their work on paternal effects in mice (most recent focuses on mothers instead of fathers so this is especially interesting).
“I am also excited to hear Ted Koditschek from Mizzou discuss the history of the classic Lamarckian idea of the “inheritance of acquired characteristics” and how it relates to findings from modern epigenetics,” Shenk said.
Schedule of events
The location of all speakers and affiliated events will be announced at lssp.missouri.edu or on the Life Sciences and Society Program — University of Missouri Facebook page.
Friday
6:30 p.m. — Topic of the talk: Sharing epigenetic research with the public. Speaker: Annie Murphy Paul, science writer and author of Origins: How the Nine Months Before Birth Shape the Rest of Our Lives.
Saturday
9 a.m. — Topic of the talk: Stress Parents: Maternal and paternal epigenetic programming of the developing brain. Speaker: Tracy Bale, professor of neuroscience and animal biology at the University of Pennsylvania.
10:30 a.m. — Topic of the talk: You are what your father ate. Speaker: Oliver Rando, professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School.
11:30 a.m. — Topic of the talk: Epigenetic inheritance and evolutionary theory: the resurgence of natural philosophy. Speaker: Massimo Pigliucci, professor of philosophy at the City University of New York.
2:15 p.m. — Topic of the talk: Environment and Autism: Past evidence, current research and future quandaries. Speaker: Irva Hetz-Picciotto, professor of public health sciences at UC Davis.
3:15 p.m. — Topic of the talk: Prenatal stress modifies the impact of phthalates on boys’ reproductive tract development. Speaker: Shanna Swan, professor of preventative medicine at Mount Sinai School of Medicine.
4:30 p.m. — Panel Session with all Saturday speakers.
Sunday
9 a.m. — Topic of the talk: DOHaD, epigenetics and cancer. Speaker: Suh-mei Ho, director of the University of Cincinnati Cancer Center, and chair of the department of environmental health.
10:30 a.m. — Topic of the talk: The epigenetics of pediatric cancers. Speaker: Joya Chandra, associate professor of pediatrics at the University of Texas MD Anderson Cancer Center.
11:30 a.m. — Topic of the talk: Before epigenetics: Early ideas about the inheritance of acquired characteristics. Speaker: Ted Koditschek, professor of history at the University of Missouri.
Affiliated events:
Exhibit running March 5-30 at the Ellis Library Collonnade. Exhibit: Generations: Reproduction, heredity and epigenetics.
1 p.m. March 9, at the Ellis Library Government Documents Section. Topic of the talk: Genes, culture and evolution. Speaker: Karthik Panchanathan, department of anthropology, University of Missouri.
3:30 o.m. March 17, at Jesse Wrench Auditorium. Topic of the talk: Profound global institutional deprivation: the example of the English and Romanian adoptee study. Speaker: Sir Michael Rutter, professor of developmental psychology at the Institute of Psychiatry at King’s College in London.
