Category Archives: Epigenetics

Epigenetics is the study of how behaviors and environment can cause changes to the way genes work

One in eightcouples have trouble getting pregnant, and the reasons for that can be varied, yet fertility is still thought of mostly as women's health issue, meaning the actual issues often go undiagnosed and untreated.

'Fertility testing and treatments almost entirely focuses on the female partner, yet 50% of infertility is due to male factors,"Andy Olson, co-founder and CEO ofInherent Biosciences, which uses epigenetics to raise the standard of care for male fertility, told VatorNews.

Epigenetics, as defined by the CDC, is "the study of how your behaviors and environment can cause changes that affect the way your genes work." That means it's actually getting to the root causes of fertility issues and going beyond the current standard of care, which Olson says is "looking at sperm with a microscope, counting how many sperm are there, and how many are swimming."

"We're aiming to raise the standard of care in male reproductive health by applying the latest in molecular technology to this gap," he explained.

On Tuesday, the company announced it raised an undisclosed amount of Series A funding from an investor group led by Propel Bio Partners, along with what the company calls "numerous stakeholders from patients to physicians and reproductive healthcare executives," including Portfolias FemTech II Fund and Alliance of Angels. This follows the company's seed funding round,from MedMountain Ventures, Kickstart Funds, Park City Angels, Rhythm VC and several angel investors, in February 2021.

Founded in 2019, the Salt Lake City-basedInherent Biosciences currently has two products currently on the market: PATH SpermQT, an epigenetic sperm quality test that can predict the need for assisted reproductive technologyl; andPATH SpermAge, which can calculate sperm's biological age.

The company works with fertility clinics and the providers in these clinics, positioning SpermQT, along with the standard semen analysis, aka looking at sperm with a microscope, for the initial evaluation of the male partner at the beginning of the fertility journey.

The reason the company chose to go after the fertility, Olson explained, is because he had friends who were going through fertility treatment, which took years and around $80,000, mostly out of pocket, only for their doctor to say they had "un-explained infertility".

"One in eight couples experience infertility, so it's a huge problem that is growing as people wait longer to have children. The female partner takes the unfair burden, but there's a big gap on the male side, and new technology that can help," he said.

Inherent Bioscience entered the market this year and has around 25 providers piloting SpermQT. The company has been able to show that aprovider doing 120 procedures spends $50,000 on Inherent's testing, they achieve an ROI of $450,000 in incremental revenue by getting patients to the procedure sooner thatis most likely to work.

"There is a very highdrop-out rateas patients do procedures that don't work. We guide treatment early to the procedure that is most likely to work and so they have fewer patients dropping out of care," said Olson.

The funding will allow Inherent to scale commercial operations and generate the further seminal data necessary to add SpermQT to the standard of care through additional prospective studies. The company will also expand its pipeline to areas such as offspring health and cancer, both of which have been shown to be influenced by epigenetics.

Go here to see the original:
Inherent Biosciences raises funding to expand fertility care though epigenetics - VatorNews

1. All-out lagoons

Sure, its cold outside in Iceland, but bubbling below the surface, geothermal energy is turning up the heat on wild-water dips in the land of fire and ice. Since the 12th century, Icelanders have soaked in silica-rich pools and hidden hot springs. But a new generation of super-spas is delivering greater comfort without making the experience any less rugged. By the same architects that created Keflaviks Blue Lagoon and the recent Geosea baths, Forest Lagoon, ensconced in rock and wood, is a timber-clad complex that seems to have emerged out of the sap-scented deep. Overlooking Valaskogur forests birch and pine, the Eyja fjord and the city of Akureyri, it includes a restaurant, two infinity pools, two swim-up bars, a cold tub and sauna. An hours drive north-east in the town of Husavik, Geoseas cliff-side seawater pools overlook a bay visited by humpbacks; while further east, near Egilsstair, Vok Baths have two pools suspended in a lake with water clean enough to drink. Down south, Reykjaviks Sky Lagoon has mastered the holistic hot-spring experience. A seven-step ritual includes a circuit of sauna, rain room and body scrub, waterfall shower and drinks at a swim-up bar: good vibes all round. Sarah Marshall

At the new Chenot Molecular Lab at Chenot Palace Weggis in Switzerland, epigenetics has gone up a notch. New mRNA-based technology at the brands sleek flagship on Lake Lucerne analyses gene activity, determines biological aging and prescribes treatment via supplements, nutrition, stress control and lifestyle changes. Inflammation, oxidative stress, hormonal imbalance and the structural integrity of tissue are highlighted. Its a modern approach, says Dr George Gaitanos, Chenots chief scientist and COO, where health is defined as what is unseen. Plus, its not all doom and gloom, because the epigenetic picture is dynamic and totally malleable, he promises. DNA is static, the 21,000 piano keys you were born with. But then you play the piano and create the melody. Are you hitting good notes, or are you too aggressive? The idea is to uncover the causes of aging and health issues years before the onset of decline. Lydia Bell

Healing Holidays can arrange a seven-night Advanced Detox programme from 6,449 per person full board; healingholidays.com. The Chenot Molecular Lab costs an extra 1,050

Sophie Delaporte / Trunk Archive

The meditation of the future is about diving deeper, a plunge into existential fathoms rather than a fey skip through the shallows of mindfulness. Mandali, a seductively minimalist new retreat in Italy, slides a side order of sybaritic comfort alongside pristine meditation instruction, with stunning views over Lake Orta inspiring guests into awed silence. At Eremito, Umbrias monastery-meets-eco hotel, meditators sleep in celluzze, or hermit cells, and the aura of peace here is palpable. Zenways life-shifting and intensive three-day retreats (in the UK, mainland Europe and the USA) are definitely not for the faint-minded. The schedule runs from dawn to nudging midnight, with 13 sessions every day. As you sit in pairs, it kicks off with a simple question: Tell me who you are? The idea is that the ego plays Twister with itself before finally giving in and settling into Zen awakening, or satori. It works and its often the beginners who get it first. Jane Alexander

Having honed Hollywoods highly insured bodies, The Ranch, known for its earthy fitness small, zesty-fresh plant-based portions and ferocious group hikes in nature has been airlifted to the sylvan surrounds of Palazzo Fiuggi. This frescoed haven outside Rome is best known for pristine medical attention and Heinz Becks carnivorous cuisine. The Ranch Italy at Palazzo Fiuggi is an unusual pairing but the proof is in the pudding. A 5.30am wake-up call heralds a stretch class followed by homemade granola and almond milk before a gruelling four-hour mountain hike that has some quitting after day one (theres more cardio and optional yoga later). Vegan fare such as macadamia Parmigiana is on the table throughout, with zero caffeine and alcohol. Daily deep tissue massages and restorative plunges into Kneipp pools take the edge off. For those who last the ride it is game-changing, with inches lost around midsections and bottoms hewn as lithe as lazio oak. Jemima Sissons

Healing Holidays can arrange a seven-night programme from 7,519 per person full board; healingholidays.com

Yoga as a gymnastic ego trip is losing its grip, while somatic movement, embodiment, fascial unwinding and pandiculation are edging in. At Yobaba Lounge in south-east France, embodiment pioneer Gertrud Keazor guides you to inhabit that soft animal of your body rather than bludgeoning you into the perfect Warrior II. Eyes are kept shut, all the better to enjoy birdsong and the soft breeze. Forget rigid adjustments follow your unfurling. You twist and twine around the mat, working deep into the fascia; its as much an emotional as a physical workout. Malabar Retreats centres on the Tibetan healing practice of Lu Jong at its outposts in Spain, Mozambique and Zimbabwe. Its a stringent practice but doesnt require bendiness or strength so works for beginners, or anyone sick of yoga-sculpt. Gone are the days of gurus, lineages and the same set of pre-defined poses, says trailblazer Gillie Sutherland, who runs retreats in Croatia and online workshops. Its about working with the bodys natural intelligence, wild and free. JA

View post:
10 wellness retreat trends to know about - Cond Nast Traveller

Dr. Kassis with members of her laboratory.Credit: NICHD

During a research career that spans four decades, NICHDs Judith Kassis, Ph.D., has learned many lessons along the way. For the last 23 years, she has headed the Section on Gene Expression at NICHD, and before that, she spent 12 years as a researcher and regulator at the Food and Drug Administration (FDA). Dr. Kassis is a leader in the field of transcriptional gene repression by Polycomb group proteins (PcG), and her laboratory explores how genes are regulated during embryonic development.

I like to follow up on unexpected results. Be open-minded about the answer, and test the hypothesis. A lot of experiments today are designed to prove a hypothesis, when you should always evaluate your idea and assumptions first, shared Dr. Kassis. Todays research environment limits ones ability to do this, but early on, I could chase whatever I wanted in the lab. When I started my graduate studies, I didnt even think about my career. I simply loved science and wanted to do it.

Childhood photo of Dr. Kassis (left) at age 1.5 with her sister Diane, age 3.Credit: Judith Kassis, Ph.D.

Dr. Kassis was the second of six children, raised in Sacramento, CA. Her paternal grandparents were Lebanese American and had an arranged marriage. They lived in North Dakota, where her grandfather owned a candy store, but the Dust Bowl forced the couple to relocate with extended family in California. Dr. Kassis father worked as a grocery store manager and insurance salesman. He later went back to school to become a certified financial planner. Dr. Kassis mother, who grew up in Minneapolis, was a college graduate and medical technician. She became a full-time homemaker soon after becoming a mother.

Looking back, Dr. Kassis is proud of carving out her career and having the opportunity to conduct research at NIH. My mom didnt work outside of the home, and I didnt know what I was going to do. Its amazing to consider where I ended up with this career when I didnt have a plan, she said.

Dr. Kassis mother was active in the American Field Service , which was known at the time for its international student exchange programs. They also had programs to learn about Native cultures, explained Dr. Kassis. When she was a senior in high school, she was an exchange student in Kotzebue, Alaska, about 30 miles north of the Arctic Circle, and spent a semester at a Bureau of Indian Affairs school. I was there during the fall and got to see the Northern lights. What I remember most is looking at the stars over the the Kotzebue Sound and the tundra, so beautiful. I was so lucky to be able to experience such a different environment and culture.

Her parents also planned independent trips for their children. When I was 18 years old, my older sister and I took Greyhound buses all over the country and visited friends of my parents. Remember, we didnt have cell phones back then, she said. Dr. Kassis and a younger brother also visited Mexico, where they took buses to Guatemala and El Salvador. My parents were very loving, generous people, who encouraged us to be curious and try different things.

For college, Dr. Kassis attended the University of California at Santa Barbara, initially with no idea of what she wanted to study. This is going to sound extremely nerdy, but I took a biochemistry class and loved it. I studied so hard that I could actually see the connections between all the different biochemical pathways, she said. For my final exam, I got an A++, and my professor helped me apply for a summer research fellowship through the National Science Foundation. It was the summer of 77, and I absolutely loved working in the lab. For her fellowship, Dr. Kassis studied malaria and enzymatic pathways at the University of California, Riverside, and then published her first paper.

During her senior year, Dr. Kassis worked in the laboratory of Leslie Wilson, Ph.D. Research was my passion, and I realized there was nothing else I wanted to do. Thats why I applied for graduate school, she explained. After graduating with highest honors and a degree in biochemistry and molecular biology, Dr. Kassis moved in 1978 to the University of Wisconsin, Madison, for her doctoral studies. I knew I wanted to move out of state, and Wisconsin had one of the best biochemistry programs in the country, she said.

Her thesis advisor was Jack Gorski, Ph.D. , one of the discoverers of the estrogen receptor. He was very smart and kind. I remember I had the choice of three topics and, after I picked one, I had to learn how to be independentthat was his philosophy. I had to think for myself, figure out who to talk to, and learn how to seek help, she said. It was a nice lab, and there were a lot of women. Overall, it was a very good experience. During those years, Dr. Kassis studied estrogen receptor recycling and met her future husband, Scott Stibitz, a fellow graduate student.

While finishing graduate school in 1983, Dr. Kassis decided to change fields. She found a new postdoctoral position in a lab headed by Patrick O'Farrell, Ph.D. , at the University of California, San Francisco, where she studied evolutionary conservation of the Drosophila engrailed gene, an important developmental gene in fruit flies that has counterparts in other living organisms, including people. It was there that she also developed a lifelong interest in how developmental genes are regulated by DNA sequences that are far away (i.e., tens to hundreds of kilobases) from where the activity begins at a transcription unit. Eventually, she would focus on the field of developmental epigenetics.

In my opinion, it was the best time to be in biology. The homeodomain was discoveredflies had it, humans had it. For the first time, people recognized that animals had so much in common at a genetic level. It was very exciting, she said. But at that time, cloning a gene and sequencing it was a whole project. For my postdoc, I cloned the engrailed gene from a related Drosophila species and sequenced it. Experiments have completely changed now. Its great that you can do more, but back then, you had more time to think.

Dr. Kassis published several postdoctoral papers and got married as she wrapped up her four-year position. I had great advisors, but there was no career mentoring back then. People didnt really talk much about careers. The biotech industry was just starting. No one asked me, Do you want to be a [principal investigator]? Everything was just about the science, she explained. Her husband received a job offer from the FDAs Center for Biologics Evaluation and Research (CBER). So, Dr. Kassis applied for jobs in the Washington, DC, area and received a job offer from CBER, too.

In 1987, she and her husband moved to the East coast, where Dr. Kassis split her time between leading a small research laboratory and regulating products made in living cells for CBER. At the time, the FDA had laboratories on the NIH campus in Bethesda, MD, and Dr. Kassis collaborated often with NIH researchers. Like all principal investigators at CBER, her progress was reviewed under NIHs tenure system, and she received tenure in 1994. The next few years brought many exciting changes.

Dr. Kassis was featured in the NIH Catalyst when she received tenure in 1994.Credit: Judith Kassis, Ph.D.

The first was related to Polycomb Response Elements (PREs). During embryonic development, some genes must be silenced or inactivated at certain times and places, for instance, in the development of different tissues and organs. This silencing is orchestrated by Polycomb group proteins (PcG), which must be recruited to the gene in question. The genes themselves contain special sequences called PREs, which bring in an intermediaryPRE DNA-binding proteinsto recruit the PcGs.

Dr. Kassis and colleagues made a string of discoveries beginning with an unexpected observation in fruit flies that enabled Dr. Kassis to easily identify PREs. She initially wanted to identify regulatory DNA by cloning it and placing it into a vector to make transgenic flies. The vector also contained a marker for eye color, a common research practice to easily identify transgenic flies from normal flies. When white-eyed flies were injected with the vector, their transgenic offspring had colored eyes. Normally, flies with two copies of the transgene (i.e., homozygotes) have a darker eye color than those that only have one copy (i.e., heterozygotes).

However, in Dr. Kassis experiments, when certain fragments of DNA were cloned into the transgene vector, the eye color of the homozygotes was lighter than that of heterozygotes. In fact, most of these homozygotes had white eyes, suggesting that the eye color marker was somehow blocked or silenced. Dr. Kassis called this phenomenon pairing-sensitive silencing. Later, she discovered that this phenomenon was caused by the PREs that she had cloned into the vector. When I presented my findings at a conference, people were very excited, and some even mentioned they had similar observations but had not followed up. I think thats how I distinguished myselfI follow up on unexpected, interesting findings, she said.

Dr. Kassis and her laboratory also discovered the first PRE binding protein, Pho, and later identified three more: Pho-like, Spps, and Combgap. The benefit of having two jobs at FDA was that I didnt have to worry about publishing in high-profile journals. I didnt have to be a bigshot. I could just do good work, explained Dr. Kassis. At that point, I was just doing what I was interested in, and I found [PREs], and it was so much fun.

Dr. Kassis with her daughter Sandy in the 1990s.Credit. Judith Kassis, Ph.D.

Dr. Kassis worked at CBER for 12 years, heading two licensing committees and her small lab. During that time, she also had her two children. It was very hard to do both the regulatory work and the research. I could see that I was going to have to make a decision, especially once you have kids. Thats like three jobs: the lab, the regulatory work, and your children, she said. She successfully applied for an opening at NICHD in 1999 to head a research lab, and she brought along her staff scientist, Lesley Brown, Ph.D., and a postbaccalaureate fellow. It was a very good time to look for a new job, and I want to highlight Lesleys contribution. Shes a transcription factor expert and discovered Pho in my lab. Im not sure I would have gotten the [NICHD] job without her and the timely publications.

NICHD colleague Paul Love, M.D., Ph.D., said that Dr. Kassis is patient, inquisitive, supportive, and always willing to listen. Scientifically, she exemplifies the model investigator. Early in her career, she identified an important but very complex question in biological science, Polycomb-mediated gene repression, and she has devoted her career to steadily chipping away at the problem. Along the way, she has come up with new insights and challenged existing paradigms. It doesnt get any better than that!

When Dr. Kassis first started her lab, she did a lot of work at the bench. Even today, you can find her observing fly embryos under the microscope and doing her own immunostaining. On some of her early papers, she was the only author because the lab was so small. It can be difficult hiring good postdocs when youre starting out, said Dr. Kassis. My advice for tenure-track investigators is to attend meetings, talk to people, talk to journal editors, and promote yourself. If youre shy, pretend you are not.

She also recommends finding a core scientific family. Dr. Kassis attends a small, regional meeting, which originally consisted of five laboratories interested in somatic chromosomal pairing in flies. We collaborate and review each others papers before submission. I also found a postdoc through this group. If youre not currently part of one, consider starting your own group.

At one point, Dr. Kassis considered taking a break from research to teach children, like her son, Zack, who have autism spectrum disorder (ASD). When he was younger, one of the hardest things we did was fight for resources. It took a lot of time and emotional energy, but things have gotten better for children and their families. Dr. Kassis also appreciates the flexibility of science that can enable a work-life balance. If I had to take my son to therapy, I could go and make up the time later. But I didnt travel to meetings as much as I might have. My husband was very supportive, so I could have gone, but I didnt want to leave them. After graduating from high school, Zack attended a program in Arizona to learn to live independently. He still resides there, with limited assistance from an agency that supports adults with ASD.

Dr. Kassis (center) on vacation with her son Zack (left) and husband Scott (right).Credit: Judith Kassis, Ph.D.

Many colleagues have benefitted from Dr. Kassis career and mentorship. Todd Macfarlan, Ph.D., recalled his early years as a tenure-track investigator at NICHD, when the intramural program reorganized into affinity groups that included several labs. Dr. Kassis became the head of our affinity group, and she demonstrated tremendous leadership, creating a fun and exciting environment for sharing our science with our close colleagues. This was a truly exceptional incubator for me, personally, and a major part of my labs early success, he said.

Mitzi Kuroda, Ph.D. , a professor at Harvard Medical School who also studies Polycomb proteins, co-authored a review with Dr. Kassis. She shared, Dr. Kassis discoveries include the foundational analysis of Pho, as well as recent elegant genetic studies on the establishment of repressive Polycomb domains and their boundaries. Her scientific acumen and creativity are especially evident in her truly unexpected discoveries of pairing-sensitive silencing and P-element homing. For these important scientific insights, as well as for her leadership and generosity, she has been irreplaceable as a mentor and colleague.

Dr. Kassis, who is now in her mid-60s, plans to retire next year. Her timeline for retirement has been influenced by various decisions and experiences over the last several years. One of the most pivotal was the unexpected death of her older sister Diane, who passed away four years ago from an aggressive cancer. We were very close and had shared a room growing up. Her death made me realize that theres more I want to do. I want to spend more time with loved ones, said Dr. Kassis. In addition to her son, she has a daughter, Sandy, who lives in Louisiana, and she enjoys visiting both of them. Dr. Kassis and her husband also raise chickens and bees and have three dogs. While I never planned on working until my 80s, I realize now that things can happen.

About eight years ago, Dr. Kassis considered switching fields but never did. Instead, she decided to tackle the unfinished projects that accumulated over the years. She also stopped hiring postdoctoral fellows once she committed to her retirement timeline. These decisions resulted in a perfect pairing of projects ideal for postbaccalaureate fellows, who generally stay for one or two years before moving on to graduate school. Dr. Kassis also does not have to concern herself with high-profile journals, which are more important for a postdoctoral fellows future job prospects.

Anna Horacek, a former postbaccalaureate trainee currently in the Molecular Cell and Biology Program at the University of California, Berkeley, is grateful for her time in Dr. Kassis lab. Notably, Dr. Kassis recognizes that each mentee is unique. While I struggled with communication and specific organizational skills, others needed support with critical thinking and designing experiments. With these objectives in mind, Dr. Kassis altered her approach for each person. She encouraged us to think of future experiments, set up one-on-one meetings to discuss professional development, and provided opportunities for us to present our research.

Currently, one of the labs most exciting projects looks at the stability of a genes on and off transcriptional state and how it is regulated. The lab is using a 79-kilobase transgene to study two epigenetically regulated enhancers, regulatory DNA sequences, important in the Drosophila wing. She and her colleagues found that deletion of either of these enhancers from the 79-kilobase transgene causes flies to have mutant wings. Surprisingly, deletion of the same enhancers from the endogenous locus (i.e., where it occurs naturally in the flys genome) does not cause the same wing mutations.

No one has moved a domain and then tried to fix it. Thats essentially what were doing, said Dr. Kassis. The only difference between the transgene and the endogenous locus is that the endogenous locus has boundaries that stop the spread of epigenetic marks and enhancer activity. These boundaries make it so that everything is concentrated inward in the gene, she explained. The lab recently found that adding these boundaries to their transgene also influenced the genes on and off transcriptional states, which fits into Dr. Kassis hypothesis. Dr. Kassis aims to wrap up this project and finish writing six papers by next year.

What Ive learned is how redundant and resilient development is, said Dr. Kassis. When you have a developmental disorder, the range of phenotype is wide because theres backup in the system. Im fascinated that even though you can make so many mutations in a gene, there are just as many redundant enhancers that enable the fly to live. But how many subtle defects do they have? Its all very interesting.

More here:
Spotlight: Women in Science: Dr. Judith Kassis on Pursuing the Unexpected - National Institute of Child Health and Human Development

A fundamental discovery about a driver of healthy development in embryos could rewrite our understanding of what can be inherited from our parents and how their life experiences may shape us.

The new research suggests that epigenetic information, which sits on top of DNA and is normally reset between generations, is more frequently carried from mother to offspring than previously thought.

The study, led by researchers from WEHI (Melbourne, Australia),significantly broadens our understanding of which genes have epigenetic information passed from mother to child and which proteins are important for controlling this unusual process.

Epigenetics is a rapidly growing field of science that investigates how our genes are switched on and off to allow one set of genetic instructions to create hundreds of different cell types in our body.

Epigenetic changes can be influenced by environmental variations such as our diet, but these changes do not alter DNA and are normally not passed from parent to offspring.

While a tiny group of imprinted genes can carry epigenetic information across generations, until now, very few other genes have been shown to be influenced by the mothers epigenetic state.

The new research reveals that the supply of a specific protein in the mothers egg can affect the genes that drive skeletal patterning of offspring.

Chief investigator Professor Marnie Blewitt said the findings initially left the team surprised.

It took us a while to process because our discovery was unexpected, Professor Blewitt, Joint Head of the Epigenetics andDevelopment Division at WEHI, said.

Knowing that epigenetic information from the mother can have effects with life-long consequences for body patterning is exciting, as it suggests this is happening far more than we ever thought.

It could open a Pandoras box as to what other epigenetic information is being inherited.

The study, led by WEHI in collaboration with Associate Professor Edwina McGlinn from Monash University and The Australian Regenerative Medicine Institute, is published inNature Communications.

The new research focused on the protein SMCHD1, an epigenetic regulator discovered by Professor Blewitt in 2008, andHoxgenes, which are critical for normal skeletal development.

Hoxgenes control the identity of each vertebra during embryonic development in mammals, while the epigenetic regulator prevents these genes from being activated too soon.

In this study, the researchers discovered that the amount of SMCHD1 in the mothers egg affects the activity ofHoxgenes and influences the patterning of the embryo. Without maternal SMCHD1 in the egg, offspring were born with altered skeletal structures.

First author and PhD researcher Natalia Benetti said this was clear evidence that epigenetic information had been inherited from the mother, rather than just blueprint genetic information.

While we have more than 20,000 genes in our genome, only that rare subset of about 150 imprinted genes and very few others have been shown to carry epigenetic information from one generation to another, Benetti said.

Knowing this is also happening to a set of essential genes that have been evolutionarily conserved from flies through to humans is fascinating.

The research showed that SMCHD1 in the egg, which only persists for two days after conception, has a life-long impact.

Variants in SMCHD1 are linked to developmental disorder Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy (FSHD), a form of muscular dystrophy. The researchers say their findings could have implications for women with SMCHD1 variants and their children in the future.

A drug discovery effort at WEHI is currently leveraging the SMCHD1 knowledge established by the team to design novel therapies to treat developmental disorders, such as Prader Willi Syndrome and the degenerative disorder FSHD.

Reference: Benetti N, Gouil Q, Tapia del Fierro A, et al. Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo. Nat Comms. 2022;13(1):4295. doi: 10.1038/s41467-022-32057-x.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

See more here:
Epigenetic Information Passed On to Offspring More Frequently Than Once Thought - Technology Networks

What if we could inherit more than our parents genes? What if we could inherit the ability to turn genes on and off?

These possibilities have come to light after our recent study, published in Nature Communications. We found information in addition to our genes was passed down from mum to offspring to affect how their skeleton develops. Thats the epigenetic information thats normally reset between generations.

ADVERTISEMENT

CONTINUE READING BELOW

Our research was in mice, the first case of its kind in mammals where a long-lasting epigenetic effect from the mothers egg is carried down to the next generation. This has lifelong consequences for that generations health.

However, we cannot be certain the equivalent epigenetic changes are also inherited in humans, including the implications for how our skeleton develops and potential impact on diseases.

Our genes (packages of DNA) tell our body to make certain proteins. But our cells also need instructions to know whether a gene should be used (switched on) or not (switched off).

These instructions come in the form of chemical or epigenetic tags (small molecules) that sit on top of the DNA. You accumulate these tags throughout your life.

Think of how punctuation marks help a reader understand a sentence. Epigenetic tags allow the cell to understand a DNA sequence.

ADVERTISEMENT

CONTINUE READING BELOW

Without these epigenetic tags, the cell might make a protein at the wrong time or not at all.

Timing is crucial in how embryos develop. If certain genes are expressed (switched on to produce a protein) too early or too late, an embryo will not develop properly.

We were interested in understanding the function of a protein in mouse eggs (ova) called SMCHD1.

By removing SMCHD1 from mouse eggs, we found mice that developed from eggs lacking SMCHD1 had an altered skeleton, with some vertebrae in the spine being disrupted.

This could only be explained by an epigenetic change due to the loss of SMCHD1 in the egg.

ADVERTISEMENT

CONTINUE READING BELOW

In particular, we looked at a set of genes known as Hox genes. These encode a series of proteins known to control how mammals skeletons develop.

Hox genes are found in all animals, from flies to humans, and are crucial for setting up our spine. Evolution has finely tuned the timing of the expression of Hox genes during embryonic development to ensure the skeleton is assembled correctly.

Our study showed that epigenetic tags established by the mothers SMCHD1 in her egg can impact how these Hox genes are expressed in her offspring.

The findings are a big surprise because almost all epigenetic tags in the egg are erased shortly after conception. Think of this a bit like a factory reset.

This means its unusual to have epigenetic information from the mothers egg carried on to her offspring to shape how they grow.

ADVERTISEMENT

CONTINUE READING BELOW

Our findings suggest even the genes you dont inherit from your mother can still influence your development.

This may have implications for the children of women with variants in their SMCHD1 gene. Variations in SMCHD1 cause human diseases such as a form of muscular dystrophy.

In the future, SMCHD1 might be a target for new medicines to alter how the protein functions and help patients with diseases caused by variations in SMCHD1. So its important to understand what consequences the disruption of SMCHD1 in the egg might have on future generations.

Scientists are now beginning to understand that the epigenetic tags added to our genes are sensitive to changes in the environment. This can mean environmental variations, such as our diet or level of physical activity, can affect how our genes are expressed. However, these changes do not alter the DNA itself.

The epigenetic state undergoes the most changes when the egg is developing and during very early embryonic development, due to the factory reset between generations. This means the embryo is more vulnerable to epigenetic, including environmental, changes during this developmental window.

ADVERTISEMENT

CONTINUE READING BELOW

As we discover more cases where epigenetic information is inherited from the mother, there may be instances where the diet or other environmental changes the mother experiences could impact the next generation.

Given that scientists can now study what happens in a single egg, we are well placed to determine how that might happen and work out what exactly we could be inheriting.

Marnie Blewitt, Head, Molecular Medicine Laboratory, Walter and Eliza Hall Institute and Natalia Benetti, PhD Student, Epigenetics and Development Division, Walter and Eliza Hall Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Also read | Children with mild COVID-19 can still develop long-term symptoms: Study

ADVERTISEMENT

CONTINUE READING BELOW

Latest Stories

Continue reading here:
New discovery shows you may inherit more from your mom than you think - EastMojo

In this weeks research news, a fat hormone that slows liver tumor growth, a genetic map to track tumorigenesis, study that shows we inherit more than expected epigenetic information from our mothers, Alzheimer linked APOE gene protects against glaucoma.

Fat Hormone Slows Liver Tumor Growth

Scientists at theUniversity of MichiganLife Sciences Institutefoundthat a hormone secreted by fat cells could slow the growth of liver tumors in mice. The research team previously used single-cell RNA sequencing to construct a liver cell atlas and map intercellular signaling in healthy and NASH mouse livers. NASH stands for nonalcoholic steatohepatitis, a type of fatty liver disease. Working to identify specific molecular changes in the NASH state of the liver cell types, they found changes in two types of immune cells that seemed to lead to the development of hepatocellular carcinoma (HCC), the most common type of liver cancer. This seemed to occur in T cells and macrophages, showing signs of acquired molecular features associated with cancer. They also identified a hormone, NRG4, secreted by fat cells that appears to protect mouse livers against NASH and HCC. By boosting NRG4 levels in the mice, they suppressed NASH liver cancer progression.

Do We Inherit More Epigenetic Information than We Think?

Researchers from theWalter and Eliza Hall Institutein Melbourne, Australia, found that more epigenetic information iscarriedfrom mother to offspring than was previously understood. Theypublishedtheir research inNature Communications.

Epigenetics is how expression of genes are switched on and off. One way this occurs, is through addition of methyl groups (a carbon atom with three hydrogen atoms attached) to the genes. Under certain situations and environments, these genes are switched on or off. These changes could be diet, trauma, whether the genes or gene alterations are inherited from the mother or the father, or other factors. But the genes were generally believed to be reset when they are passed on to offspring.

Part of the team's research found that a specific protein in the mother's egg can affect the genes behind the skeletal patterning of offspring. SMCHD1 is an epigenetic regulator discovered in 2008. Hox genes, which are essential for normal skeletal development control the identity of each vertebra during embryonic development. SMCHD1 prevents the Hox genes from activating too soon. They found that the amount of SMCHD1 in the mother's egg affects Hox gene activity and influences the patterning of the embryos. Without maternal SMCHD1 in the egg, offspring were born with altered skeletons.

"It took us a while to process because our discovery was unexpected," Marnie Blewitt, Ph.D., chief investigator and Joint Head of the Epigenetics and Development Division at WEHI, said. "Knowing that epigenetic information from the mother can have effects with life-long consequences for body patterning is exciting, as it suggests this is happening far more than we ever thought. It could open a Pandora's box as to what other epigenetic information is being inherited."

A Genetic Map of Tumors Show How They Grow

Researchers at theUniversity of Oxfordused anew techniquecalled spatial transcriptomics to map out the genetic changes of a whole prostate, including both healthy and cancerous cells. The technique grouped cells according to similar genetic identities. Surprisingly, they found that areas of what were thought to be healthy tissue already had genetic characteristics of cancer. What was originally thought to be healthy tissue showed mutations specifically linked to cancer. Researchers also analyzed more than 150,000 regions including prostate, breast cancer, skin, lymph node and brain tissue. They then developed an algorithm to track groups of cells with similar genetic changes in their specific location.

Alzheimer's Linked APOE Gene and Glaucoma Protection

The most prominent gene associated with the risk of Alzheimer's disease is the APOE4 gene variant. However, this same gene variant decreases the risk of glaucoma, an eye disease. Researchers at Mass Eye and Ear and Brigham and Women's Hospital and Mass General Brigham alsopreventedthe destruction of neurons in the eyes of mice with glaucoma by using a drug that targeted the APOE signaling pathway. Specifically, APOE4 blocks a disease cascade that causes the destruction of retinal ganglion cells in glaucoma. Separately, in a mouse model, they used a drug called Galectin-3, which is regulated by the APOE gene, to prevent the death of retinal ganglion cells, which cause loss of vision in glaucoma.

"Our research provides greater understanding of the genetic pathway that leads to irreversible blindness in glaucoma, and importantly, points to a possible treatment to address the root cause of the vision loss," Milica Margeta, M.D., Ph.D., lead author and a glaucoma specialist and scientist at Mass Eye and Ear, and assistant professor of ophthalmology at Harvard Medical School, said. "This study shows that the APOE-mediated disease cascade is clearly harmful in glaucoma, and that when you interfere with it genetically or pharmacologically, you can actually stop the disease

Go here to see the original:
Research Roundup: Fat Cell Hormone Slows Liver Tumor Growth and More Research News - BioSpace

An ongoing effort to create detailed molecular atlases of individual cells in different tissues aims to better understand how diseases develop. Now, a team of researchers from Yale and Karolinska Institutet, has developed a technology that brings that goal one step closer.

How cells function in tissue depends upon their local environments. Mapping the molecular properties of cells while acquiring their exact location within a tissue is essential for a better understanding of disease. Rong Fan, professor of biomedical engineering at Yale, and Goncalo Castelo-Branco, professor of glial cell biology at Karolinska Institutet, led a team of researchers in developing a new technology to do this. It allows them to define which regions of the chromatin - the complex of DNA and proteins packed within the nucleus of a cell - are accessible genome-wide in cells at specific locations in a tissue. This chromatin accessibility is required for genes to be activated, which then provides unique insights on the molecular status of any given cell. Combining the ability to analyze chromatin accessibility with the spatial location of cells is a breakthrough that can improve our understanding of cell identity, cell state and the underlying mechanisms that determine the expression of genes - known as epigenetics - in the development of different tissues or diseases. The results are published today in Nature.

Now we can identify the cell types to build a spatial cell atlas based in chromatin accessibility, Fan said. We can directly see the cell types at an epigenetic level either for a better definition of cell states or the discovery of cell types.

The researchers profiled both mouse and human tissues using a technique known as spatial-ATAC-seq. Applying this technique to brain tissue revealed the intricate development process of different brain regions. They also applied it to the human tonsil tissue, which provided insight into the organization of immune cell types.

Well get an unbiased global view, and a much finer resolution view, of all possible cell states, and more importantly, see where they are in a tissue, Fan said. Its a powerful tool for building cell maps and cell atlases.

Yanxiang Deng, a postdoctoral associate in Fans lab and lead author of the study, said that by using the new method, they were able to identify the epigenome of cell types in the mouse brain tissue in their native location.

Applying spatial ATAC-Seq in diseased tissues might allow us in the near future to identify transitions between epigenetic states in specific cells in the context of the disease niche, which will give insights of the molecular mechanisms that mediating the acquisition of pathological cellular states, added Castelo-Branco.

An ambitious global initiative has been undertaken to map out all the different cell types across all of the human organs and different tissue types. Single-cell sequencing has been critical to this effort but it is hard to map the location of cell types to the original tissue environment. This work for the first time allows for directly observing cell types in a tissue as defined by global epigenetic state.

The studys other authors are Marek Bartosovic, Sai Ma, Di Zhang, Petra Kukanja, Yang Xiao, Graham Su, Yang Liu, Xiaoyu Qin, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Mina L. Xu, Stephanie Halene, Joseph E. Craft, Kam W. Leong, and Maura Boldrini.

Continue reading here:
New Technology to Understand Cell Types and How Diseases Develop - Yale University

Many experts have raised concerns over the concept of reviving extinct species in a vastly different environment

By Kiran N. Kumar

While dinosaurs or mammoth elephants remain extinct, their revival remained confined to fiction or Hollywood movies so far. But heres a biotech and genetic engineering startup Colossal Biosciences that has announced plans to de-extinct the Tasmanian tiger using gene-editing technology.

The Tasmanian tiger (thylacine), a carnivorous dog-like marsupial with stripes was the recent species of the family Thylacinidae on record by the European settlement in Australia. A local species, the marsupial carried its babies in a pouch just as kangaroos or koalas do.

When they were chasing poultry for food, the hunt for them with heavy bounties as reward in the 19th century led to their extinction by the 1930s. Now the new biotech startup is keen to revive this extinct species, almost a century later, using genetic engineering, extraction of old DNA, and artificial reproduction.

Read: One hour after death, life restored in dead pigs tissues (August 4, 2022)

The genome for the species, sequenced from DNA recovered from a 108-year-old specimen kept at Australias Victoria Museum, is available for researchers led by Prof. Andrew Pask at the Thylacine Integrated Genetic Restoration Research (TIGRR) Lab and professor of epigenetics biosciences at the University of Melbourne.

The team plans to use IVF and gestation without a surrogate, with Colossal deploying the CRISPR gene editing and computational biology capabilities to reproduce thylacine DNA.

We can now take the giant leaps to conserve Australias threatened marsupials and take on the grand challenge of de-extincting animals we had lost, Professor Pask said. With this partnership, I now believe that in ten years time we could have our first living baby thylacine since they were hunted to extinction close to a century ago.

Jurassic Park ConcernsThe project has received wider support among celebrities such as Chris Hemsworth and Paris Hilton who have extended support to revive the Tasmanian tiger but not without concerns.

Many experts have raised concerns over the concept of reviving extinct species back to life in an environment that was vastly different from the time when they existed and wandered on the earth, a fact captured in the Jurassic Park franchise.

Pask and Colossal, however, insist that the Tasmanian tigers return would enforce rebalance in Australias ecosystem, which has a record extinct species.

Without an apex predator, ecosystems plunge into a series of cascading trophic downgrading effects, leading to the spread of disease, an increase in wildfires and invasive species, a reduction in carbon sequestration, and a disruption to natural biogeochemical cycles, said the startup.

TIGGRS partnership with Colossal will influence the next generation of Australias marsupial conservation efforts and combat increasing extinction events caused by invasive species and climate change, said Pask.

Our efforts to protect the endangered Northern Quoll long threatened by the invasive cane toad native to South and Central America will also be aided by this partnership, as we could produce Northern Quolls with a slight genome-edit making them resistant to cane toads, giving Quolls the same evolutionary benefit of the many South and Central American animals resistant to cane toad-poison, he said.

Original post:
De-extinction? Plans to revive Tasmanian tiger triggers... - The American Bazaar

Epigenetic mechanisms, which include DNA methylation, histone modification, and microRNA (miRNA), can produce heritable phenotypic changes without a change in DNA sequence. Disruption of gene expression patterns which are governed by epigenetics can result in autoimmune diseases, cancers, and various other maladies. Mechanisms of epigenetics include DNA methylation (and demethylation), histone modifications, and non-coding RNAs such as microRNAs. Compared to numerous studies that have focused on the field of genetics, research on epigenetics is fairly recent. In contrast to genetic changes, which are difficult to reverse, epigenetic aberrations can be pharmaceutically reversible. The emerging tools of epigenetics can be used as preventive, diagnostic, and therapeutic markers. With the development of drugs that target the specific epigenetic mechanisms involved in the regulation of gene expression, development and utilization of epigenetic tools are an appropriate and effective approach that can be clinically applied to the treatment of various diseases.

Keywords: Checkpoints; Cytokines; DNA methylation; Histone modification; Immune dysfunction; Signaling pathways; miRNA.

Originally posted here:
Epigenetics in Health and Disease - PubMed

Editors-in-Chief

Lucia Altucci,Universitdegli Studi della Campania, ItalyMarianne Rots,University Medical Center Groningen, Netherlands

Encompassing the broad spectrum of epigenetics research frombasicresearch to innovations in therapeutic treatments,Clinical Epigeneticsis a top tier, open access journal devoted to the study of epigenetic principles and mechanisms as applied to human development,disease, diagnosis and treatment. The journal particularly welcomes submissions involving clinical trials,translational research,new and innovative methodologies and model organisms providing mechanistic insights. The journal is divided into the following sections:

For more information on the section aims and scope visit our sectioninformation page. If you are unclear which section would be best suited to your submission, we invite you to submit a pre-submission inquiry by selecting the Contact Us option here.

Manuscripts focusing on differential RNA expression levels (coding or non-coding) or on RNA modifications cannot be considered for publication in Clinical Epigenetics since these aspects are not part of epigenetics per se.

In general, non-coding RNAs affect their target genes at the RNA level, which classifies these molecules as post-transcriptional gene expression regulators. The chromatin effects induced by some ncRNA do not yet justify this, to be included as a general mechanism of action of non-coding RNAs. Similarly, although modifications of RNA molecules resemble modifications of DNA or histone proteins, so do post-translational modifications of non-chromatin proteins. As such, RNA modifications are a novel class of markers, but they are not different from general posttranslational protein modifications (which also are not considered part of epigenetics).

For manuscripts on non-coding RNAs or RNA modifications to be considered for publication in Clinical Epigenetics, the authors must provide at least one of the following:

Manuscripts reporting on straightforward bioinformatic analyses of publicly accessible databases only, cannot be considered for publication in Clinical Epigenetics, unless the manuscript presents:

In October 2011, Clinical Epigenetics became a fully open access journal and is now published as part of BioMed Central's portfolio of journals. To view the journal's content prior to this transition, please see SpringerLink.

Continued here:
Clinical Epigenetics | Home page