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.
Beneath a North Carolina field in 1954, a tiny worm inched its way through the soil and butted against a soybean root. The worm pierced the plant, slipped inside and inserted a needle-like appendage into a cell. It pumped a mixture of proteins into the root cell and waited for the potent blend to take effect on the unsuspecting soybean.
Since the first detection of soybean cyst nematode (SCN) in the US, the worm Heterodera glycines has spread to about 80 percent of American soybean fields. In Missouri, SCN attacks soybeans in almost every county and causes decreased yields even in robust, healthy-looking fields. Nationwide, SCN wreaks havoc to the tune of $1.2 billion per year, making it by far the most costly soybean pest.
Despite the hefty toll, farmers still depend on the same small handful of resistant soybean varieties to combat SCN that they have used for years. But those natural defenses are becoming less effective as nematodes evolve.
“More than 90 percent of the soybean cultivars that farmers plant derive their resistance from a single source,” said Melissa Mitchum, a plant nematologist at the University of Missouri Bond Life Sciences Center and Division of Plant Sciences faculty member in the College of Agriculture, Food and Natural Resources. “Consequently, this has led to widespread virulence in the pathogen population, thereby reducing the effectiveness of those resistant cultivars.”
But in the past 10 years, researchers studying SCN have made numerous breakthroughs, unlocking the secrets of the nematode and exploring how the worm interacts with host plants. Now, scientists are poised to bring that knowledge from the laboratory to the field.
Found in translation
Relatively little was known about SCN a decade ago.
Scientists could determine the type of nematode in a soil sample and had just figured out the cocktail of proteins a nematode pumps into the soy root cell that transform it into a syncytium, or feeding cell.
Working in part with funding from commodity boards and farmer checkoff dollars, researchers around the country made breakthrough after breakthrough, deepening our understanding of SCN and equipping scientists with new tools to fight the pest.
That money helped scientists sequence the soybean genome, draft a SCN genome and pinpoint important soy and SCN genes.
Checkoff investments continued to pay dividends in 2012 when Mitchum and colleagues cloned the first gene linked to natural soybean cyst nematode resistance. This breakthrough is one key step in moving science from the laboratory into the field. With a SCN resistance gene in hand, new avenues for creating soybean varieties that fight off the nematode are opening up.
But other areas of research also hold promise in the struggle against soybean cyst nematode’s parasitic ways.
Mitchum’s group also identified the plant receptors that recognize and respond to the blend of proteins an attacking nematode inserts into a plant. In a recent project published in Plant Biotechnology Journal, Xiaoli Guo, a postdoctoral fellow in Mitchum’s lab demonstrated that silencing those receptors in soybean roots helped the plant resist SCN.
This work has implications for more crops than just soybeans: Working with collaborator Xiaohong Wang at Cornell, Mitchum’s group used their understanding of plant receptors to develop a potato resistant to potato cyst nematode.
A roadmap for discovery
To build on the momentum of recent research, experts drafted a roadmap for the next decade of nematode research. Their goal, Mitchum said, is to address the challenge of translating these research breakthroughs into something tangible for the farmer.
With support from state farmer run organizations such as the Missouri Soybean Merchandising Council, the North Central Soybean Research Program and the United Soybean Board, researchers are formulating teams that “bring together commodity, industry and university funding to develop collaborative, interdisciplinary, multistate projects,” said Mitchum.
And there’s plenty of scientific firepower to advance research: MU’s College of Agriculture, Food and Natural Resources alone has more than 90 faculty studying plant science, plant genetics and other areas of agriculture-related science.
The scientists’ plan for the next 10 years involves a blend of molecular research, plant breeding, population biology and outreach. Researchers will focus on refining the existing draft SCN genome, which will help to develop a quick, inexpensive test for HG type and eventually contribute to understanding of how SCN overcomes a plant’s resistance. They’ll create an “atlas” of SCN genes researchers can use to block the pest. Updating yield loss estimates and mapping SCN distribution will also give scientists a better idea of the nematode’s national impact. Other efforts will allow breeders to incorporate new sources of resistance into commercially-available varieties, refine the use of non-host species to control SCN and develop a pipeline for creating and testing transgenic SCN-resistant soybeans. Finally, videos, webinars and training modules will help scientists, students and producers take advantage of new discoveries and techniques.
Onward with research
A thorough understanding of SCN resistance and virulence starts with basic research and then moves into the field. “We all need to come together to transfer this knowledge to the breeder,” Mitchum said, “and from there it gets out to the farmer.”
Her lab recently received a National Science Foundation grant to continue their work on soybean protein receptors. Specific targeting of the receptors is just one potential strategy for producing new kinds of SCN-resistant plants. A second grant, from the National Institute of Food and Agriculture, will allow the lab to continue refining their understanding of how SCN proteins overcome a host plant’s defenses. To that end, Mitchum’s graduate student Michael Gardner is identifying the genetic blueprint of the different SCN types present in Missouri fields.
“If we better understand nematode populations and what makes those populations distinct, we can better advise farmers confronted with virulent nematodes,” Gardner said. “We’ll be able to go one step beyond the HG type test and understand how nematodes are able to adapt in the long term, not just the next growing season.”
But these breakthroughs do little good unless they then become useful tools for breeders and ultimately farmers. To that end, Mitchum and other researchers will help breeders use research results to produce soybeans with durable resistance. They‘ll also develop guides so farmers can easily incorporate new technologies and management strategies into their farms.
It’s important for farmers, breeders and researchers to take a unified approach to fighting SCN, Mitchum said, because a tactic that seems successful at first could backfire.
For instance, combining resistance genes in a single soybean variety could actually be harmful. “When we deploy it in the field, we select for nematodes that can overcome multiple types of resistance,” Mitchum said.
A better approach might be to perfect varieties with distinctive resistance mechanisms and insure durable resistance by rotating among the resistant varieties and non-host crops.
“It’s similar to taking antibiotics,” Mitchum said. “Improper use and overuse selects for resistance.” The strategic planning document should help everyone working with soybeans and SCN leverage and build upon new knowledge.
Despite all the research and recent breakthroughs, there remains only one certainty in the ongoing arms race between soybeans and SCN: “It is highly unlikely that we will eradicate it.” Mitchum said, “We’re going to have to find new strategies to protect and bolster soybean yields.”
Thanks to the efforts of researchers such as Mitchum, in the future SCN might be a little easier to get along with.
University of Missouri Plant Nematology Laboratory: An extensive legacy
Bob Heinz spent his last day at work in December surrounded by nematodes. Heinz served as Mitchum’s research specialist and coordinator of the Plant Nematology Laboratory, where he processed soil samples, responded to growers and assisted researchers. After 35 years on the job, he’s retired, and Amanda Howland is now filling his shoes. The scientists and farmers who’ve worked with Bob over the decades thank him for his dedication and wish him luck in his retirement. And Amanda: Welcome aboard.
The Plant Nematology Lab, housed within Mitchum’s lab at MU, represents a successful model for how research, teaching and extension program integration can promote interdisciplinary collaboration. Such an approach helps maintain an effective pipeline that brings research-based information and resources from MU to Missourians. The lab offers an array of tests that help farmers understand and manage nematode populations. The available tests include:
–Vermiform Nematode Identification: Soybean Cyst? Root Knot? Lesion? Find out what kinds of nematodes are in your fields with this test.
–Soybean Cyst Nematode Egg Count: This procedure provides an estimate of the number of SCN eggs in your field.
–Soybean Cyst Nematode HG Type Test: Different types of SCN have overcome various sources of soybean resistance. A HG type test will help you determine the best source of resistance for the particular type of SCN in your field.
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 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.
“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.
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.
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.
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.
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.
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.