Category Archives: Human Genetics

Dr. Huda Zoghbi, a neurologist whose work has revealed the molecular basis of neurological disorders, is the recipient of the 2017 Switzer Prize awarded by the David Geffen School of Medicine at UCLA for excellence in biological and biomedical sciences research.

Zoghbis lab at the Baylor College of Medicine identified a gene mutation that causes Rett syndrome, a severe genetic disorder that mostly affects girls. After a short period of apparently normal development, the disorder causes them to lose language and motor skills, typically by 18 months of age. The discovery paved the way for a genetic test to diagnose the disorder. The same gene mutation can also cause autism, juvenile-onset schizophrenia and other neuropsychiatric disorders.

Zoghbi also discovered the molecular mechanism of spinocerebellar ataxia 1, a neurodegenerative disorder in which peoples balance and coordination progressively worsens. Zoghbi and collaborator Harry Orr identified the gene mutation responsible for the disorder.

These and other discoveries by Zoghbi have opened up new areas of inquiry with the potential to advance diagnoses and treatments for Alzheimers disease, Parkinsons disease and other neurological diseases.

Dr. Zoghbis extraordinary work represents a powerful example of the direct impact that biological and biomedical research have on the lives of patients, said Dr. Kelsey Martin, dean of the Geffen School of Medicine.

Zoghbi is scheduled to deliver the Switzer Prize lecture at UCLA on Feb. 16, 2018. She will receive a $25,000 honorarium and a medallion.

Im honored to accept UCLAs Switzer Prize on behalf of the patients and the families to whom I am committed, and also on behalf of my many research collaborators and trainees, she said.

Zoghbi is a Howard Hughes Medical Institute investigator, a professor at the Baylor College of Medicine and the founding director of the Jan and Dan Duncan Neurological Research Institute at Texas Childrens Hospital in Houston. She has faculty appointments in the departments of pediatrics, molecular and human genetics, neurology and neuroscience.

A native of Beirut, Lebanon, Zoghbi fled the civil war in her home country in the mid-1970s while a medical student at the American University of Beirut. She earned a medical degree at Meharry Medical College in Nashville and went on to become chief resident in pediatrics at Baylor College of Medicine and Texas Childrens.

After years of treating patients, Zoghbi became fascinated with the origins of disease and committed to a three-year fellowship in molecular genetics to acquire research training.

She is a member of the National Academy of Sciences, the National Academy of Medicine and the American Association for the Advancement of Science.

Zoghbi is the recipient of a number of other prestigious awards, including the Breakthrough Prize in Life Sciences, the Shaw Prize in Life Science and Medicine and the Canada Gairdner International Award.

See the article here:
David Geffen School of Medicine at UCLA names winner of Switzer Prize for research excellence - UCLA Newsroom

Sonia Vallabh lost her mother to a rare brain disease in 2010, and then learned she had inherited the same genetic mutation. She and her husband, Eric Minikel, went back to school to study the family of illnesses prion diseases in the hope of finding a cure for Sonia. Kayana Szymczak for NPR hide caption

Sonia Vallabh lost her mother to a rare brain disease in 2010, and then learned she had inherited the same genetic mutation. She and her husband, Eric Minikel, went back to school to study the family of illnesses prion diseases in the hope of finding a cure for Sonia.

In 2010, Sonia Vallabh watched her mom, Kamni Vallabh, die in a really horrible way.

First, her mom's memory started to go, then she lost the ability to reason. Sonia says it was like watching someone get unplugged from the world. By the end, it was as if she was stuck between being awake and asleep. She was confused and uncomfortable all the time.

"Even when awake, was she fully or was she really? And when asleep, was she really asleep?" says Sonia.

The smart, warm, artistic Kamni just 51 years old was disappearing into profound dementia.

"I think until you've seen it, it's hard to actually imagine what it is for a person to be alive and their body is moving around, but their brain is not there anymore," says Eric Minikel, Sonia's husband.

In less than a year, Sonia's mom died.

An autopsy showed Kamni had died from something rare a prion disease. Specifically, one called fatal familial insomnia because in some patients it steals the ability to fall asleep.

Basically, certain molecules had started clumping together in Kamni's brain, killing her brain cells. It was all because of one tiny error in her DNA an "A" where there was supposed to be a "G," a single typo in a manuscript of 6 billion letters.

Sonia sent a sample of her own blood to a lab, where a test confirmed she inherited the same mutation. The finding threw the family into grief all over again.

"But that grieving period sort of started to resolve within about a week or so," she says. "And we weren't in crisis anymore. We were finding our way toward a new normal, where this was something that we were going to have to live with and deal with and learn more about."

Today, Sonia and her husband live and work in Cambridge, Mass., where they are both doctoral students in the lab of Stuart Schreiber, a Harvard professor of chemistry and chemical biology. Over the past several years, the couple has completely redirected their careers and their lives toward this single goal: to prevent prion disease from ever making Sonia sick.

The two wear bright colors and laugh easily. When they answer my questions, they look at each other instead of at me. They like complicated board games, urban walks and efficient cooking. They are thinkers and problem solvers, which is why, when Sonia got her genetic test results, it changed everything.

The change

"It didn't happen all at once," Sonia says. "There wasn't a day when we woke up and said, 'OK let's change everything about our lives.'"

At the time, Sonia, who has a Harvard law degree, had just started a new job as a legal consultant. Eric was a transportation analyst.

But they couldn't stop thinking about Sonia's test result. They started researching prion diseases online, and invited over friends who are biologists and chemists, to help them understand the science.

"And around that time," Sonia says, "we both enrolled in night classes as well," in subjects like biology and neuroscience.

They were hungry to learn more as quickly as possible; the night classes weren't enough.

"I was basically fresh out of law school and started walking into classes at MIT during the day because this was kind of all I could think about," says Sonia, who at the time wore sneakers every day so that she could rush between work, classes, and a neuroscience lab at Massachusetts General Hospital. She'd started volunteering there, thanks to a professor from one of her classes, and mentors in the lab who helped her learn everything from how to use a pipette to how to work with human brain cells.

"And from there, this is where things happened surprisingly quickly," Sonia says.

Eric and Sonia prepare materials for an experiment measuring prion protein in spinal fluid. They're both third-year Harvard graduate students doing research at the Broad Institute in Cambridge, Mass. Kayana Szymczak for NPR hide caption

Eric and Sonia prepare materials for an experiment measuring prion protein in spinal fluid. They're both third-year Harvard graduate students doing research at the Broad Institute in Cambridge, Mass.

The couple started a nonprofit, Prion Alliance, in hopes of raising money for research. Sonia left her legal job to work in the Mass General lab full-time as a technician. Then, Eric left his job and joined a genetics lab, applying his skills in coding to analyzing genetic data, rather than transportation data.

"I was getting left behind!" he says. "Sonia was out there doing all this science. It was her day job now and I was still in my old career and, you know, it was a good job and all, it was meaningful, but it wasn't the mission that it was increasingly clear that we were going to be on."

Just months after they'd finished grad school in law and urban planning, the pair went back to graduate school, this time in biomedical sciences to study prion diseases.

"You are talking to two third-year graduate students," says Eric.

Life as scientists

The two now share an office and a lab bench, under Schreiber's supervision, at the Broad Institute of MIT and Harvard.

"There's a date in the future when Sonia will get the first dose of the drug that's going to save her life," Eric says. "What can I do today that brings that date closer to the present?"

A posted printout of an email says: "Let's just blast forward and solve problems as they become real and as they need immediate solutions." It's a note Schreiber sent the pair at one point when they were worrying about bureaucratic hoops they had to jump through.

"I thought it was a good philosophy, so we printed it out and put it on the wall," says Eric.

Sonia and Eric are "the best of humanity" Schreiber tells Shots. "Their story is, of course, remarkable, and they personify the concept of patientscientists. But their deep understanding of science and ability to innovate and execute on one of the hardest challenges in biomedical science are breathtaking."

Schreiber says that his lab, like many others in biomedicine, has long included researchers who are physicians as well as scientists; that dual training and experience brings an important perspective to the research, he says.

"But the last decade has seen the emergence of patientscientists including Sonia and Eric, but also others in my lab," he says. "And this has had an even greater impact on the lab. They remind us of our mission to understand and treat human disease."

Still, it's really hard to cure diseases especially conditions like this one, because the usual way scientists look for a treatment isn't going to work.

Sonia is 33 years old. On average, people with the kind of genetic mutation she has usually start to show symptoms at age 50. But they could surface at any time. Symptoms of fatal familial insomnia have set in as early as age 12 and as late as 84. Once they do, it's a rapid decline like Alzheimer's disease on fast-forward.

"You're healthy, you're healthy, you're healthy and then you're falling off a cliff," says Sonia. "You wait a little bit too long, and that patient is gone. We need to get out ahead of it aggressively."

The challenge

They need to keep Sonia from getting sick in the first place. And they need to do it quickly. But right now, Sonia appears to be just fine, and that's actually one of the first obstacles.

Across medicine, there is an understandable resistance to testing experimental drugs on healthy people. That's why, traditionally, drug trials go something like this: Take a group of people who are sick, give some of them an experimental medicine, and wait to see if it makes them get better, live longer, or decline more slowly than people who didn't get the drug.

But Sonia has to convince the medical establishment that, especially in the age of genetics, some people who seem perfectly healthy should be considered patients.

Sonia measures prion protein in mouse cells. In prion disease, certain proteins in the brain start clumping together, which eventually kills neurons. Kayana Szymczak for NPR hide caption

Sonia measures prion protein in mouse cells. In prion disease, certain proteins in the brain start clumping together, which eventually kills neurons.

"We have to be willing to act upstream of what we would traditionally call 'illness'," she says.

It's a shift in mindset that she had to come to grips with, personally.

"I feel very lucky to be healthy today," she says. "But I hold a sort of dual reality understanding of my own health, which is that I'm healthy today but very seriously at risk for a very serious disease."

Others in the medical field, like Dr. Reisa Sperling, who studies Alzheimer's disease, are making the same mental shift as they think about the best time to intervene.

"Alzheimer's disease is a terrible disease. Many people fear it more than cancer," says Sperling, a neurologist with Brigham and Women's Hospital and Massachusetts General Hospital.

Like Sonia and Eric, she, too, is on a quest to prevent even the first symptoms of a terrible brain disease.

Sperling is now enrolling people whose brain scans show they might be in the very early stages of Alzheimer's in a clinical trial to test an experimental drug treatment. And she's planning another study in people as young as 50 who have no noticeable symptoms, but are at high risk of developing them.

"It really does primarily come down to thinking about disease as beginning years before symptoms," says Sperling. "If we can shift that thinking not just in Alzheimer's disease, but in rarer diseases like prion diseases I think this is the way we win the war."

But before any of that can happen with a prion disease, there's the problem of actually doing the science to find a good candidate drug.

The plan

Researchers don't have one in hand yet, but they have a clear idea of what it should look like, based on studies in mice. Sonia and Eric already are talking to pharmaceutical companies that may be involved in running human trials in the future, and have requested a meeting with the Food and Drug Administration to talk about what a trial should involve.

Other efforts at treating prion disease have focused on preventing the misfolded proteins from killing brain cells, or on preventing them from accumulating. Sonia and Eric have a different approach.

"We're really interested in preventing the misfolding in the first place," says Sonia.

"Sonia's brain is producing this mutant protein," Eric says. "But as far as we know it's not misfolded yet, and the disease process hasn't started. I want her brain to be producing half or less of the amount of that protein as she is [producing] right now, because we know that less is better."

Essentially, they want to muffle the faulty gene in order to reduce the amount of prion protein floating around in Sonia's brain.

But a key question right now is this: Say they make the right drug and give it to Sonia and others with her type of mutation. If the goal is to change nothing about her current health, then how will they know it's actually working?

A traditional clinical trial is out of the question, Eric says.

It would be unethical and untenable he says, to "just treat half of the people with a drug and half with placebo and then wait 30 years to see when they die."

Not only would that kind of experiment condemn some patients to terrible death, it would also be wildly expensive and require thousands of participants. There are only a few hundred people in the U.S. with prion disease mutations.

"Instead, we need a biomarker," Eric says. "We need some laboratory test that we can run on a living human to see if the drug is having its effect."

The answer, Sonia and Eric hope, could be in a very cold refrigerator in the lab where they work. It's full of samples of spinal fluid. In mouse studies, at least, reducing prion protein in the brain seems to delay disease progression.

So, Sonia and Eric are now studying samples of spinal fluid from all sorts of people from people who already have symptoms of prion disease, from others like Sonia (who have mutations for prion disease but no symptoms yet) and from healthy controls. The aim is to establish how the levels of protein in the samples change over time, to figure out if protein levels would be a good enough measure to say, "Yes, this drug works."

"We have strong evidence that 50 percent [reduction] if we could achieve that would be protective," says Sonia, based on preliminary findings in mice.

Others are optimistic, too

Sonia and Eric are organized, hardworking, and efficient. Ultimately, for them, failure is not an option. But on a day-to-day basis, failure is what science is all about.

Ericl and Sonia on their wedding day in 2009. Zamana Photography/Courtesy of Sonia Vallabh hide caption

Ericl and Sonia on their wedding day in 2009.

"In biology, if everything you did one day goes wrong, and then you figure out why it went wrong, that was a good day," says Eric, who chronicles their struggles on a blog.

It's an achingly slow process. But Eric thinks they will do it they'll find a drug.

"I'm an optimist that we'll get there in our lifetime," he says, "but not this year and not next year."

He's not alone in his optimism. Sonia and Eric have some powerful colleagues who believe the couple can pull it off colleagues like Eric Lander, a renowned mathematician, geneticist and molecular biologist. He started the Human Genome Project and founded the Broad Institute where Sonia and Eric now work.

"This is not pie in the sky," says Lander. "I see a path forward for multiple shots on goal. All you have to do is get one through."

Fifteen years ago, he says, solving this puzzle would have seemed impossible. But now he believes the science, the technology, and the knowledge about what certain mutations mean for a person's health have made defeating prion disease possible.

"Human genetics and molecular medicine are reaching a point of maturity where they're becoming much more powerful," he says. "It's exciting and important and there's nobody who's more motivated than somebody who's going to be affected by the disease themselves."

One small success

In one way, Sonia and Eric have already stopped the disease in its tracks.

Sonia is very pregnant. She's due in July to have a daughter a daughter without a mutation for prion disease. That's something the couple made sure of by screening embryos after in vitro fertilization.

A collection of mementos from Sonia and Eric's wedding in 2009 hangs on a wall in their apartment. Kayana Szymczak for NPR hide caption

A collection of mementos from Sonia and Eric's wedding in 2009 hangs on a wall in their apartment.

So, they've stopped the transmission of prion disease in Sonia's line of the family. And in a way, that's a gift from Sonia's mom, Kamni, the couple says.

"If my mom was still alive, we wouldn't know any of this and we wouldn't have had the opportunity to choose to have a mutation-negative baby," says Sonia. "But, tragically, it also means that they'll never meet."

Sonia and Eric hope that, by the time their daughter is in elementary school, Sonia will be taking an experimental drug that could keep her as healthy as she is today.

The rest is here:
A Couple's Quest To Stop A Rare Disease Before It Takes One Of Them - NPR

Forbes

Can Algae Replace Oil Wells? Craig Venter And Exxon Take A Step Toward Saying 'Yes' Forbes Synthetic Genomics (SGI) was founded in 2005 by Venter, shortly after he had become famous racing the U.S. government to map the first human genome and then ended up ousted from Celera Genomics, the company he founded to study human genetics. and more »

See the original post:
Can Algae Replace Oil Wells? Craig Venter And Exxon Take A Step Toward Saying 'Yes' - Forbes

Writing in The Hindu, Tony Joseph has claimed that genetics has very sure-footedly resolved the debate about whether there was a migration of Indo-European people (Aryans) into the subcontinent around 2000-1500 BCE apparently, the unambiguous answer is yes. To anyone with a nodding acquaintance with the literature in the area, such an assertion is unfounded. Given the sheer importance of this topic to Indian history, it is necessary to challenge Josephs one-sided presentation of facts. There also seems to be much that is questionable in his very approach, and this deserves scrutiny.

Conclusions decided upon in advance?

Ironically, after saying that the dominant narrative so far that genetics had disproved Aryan immigration had not been nuanced, he abandons nuance himself.

Noting the clear slant in his article, and his quoting of Razib Khan, who was sacked as a columnist by the New York Times apparently for racist views, I got in touch with Dr Gyaneshwer Chaubey, senior scientist at the Estonian Biocentre, Tartu, and a widely-published scholar in the area. Indeed, Chaubey is a co-author with Peter Underhill (whom Joseph quotes) of the 2015 study on the R1a haplogroup that Joseph cites in his article.

To my surprise, it turned out that that Joseph had contacted Chaubey and sought his opinion for his article. Chaubey further told me he was shocked by the drift of the article that appeared eventually, and was extremely disappointed at the spin Joseph had placed on his work, and that his opinions seemed to have been selectively omitted by Joseph a fact he let Joseph know immediately after the article was published, but to no avail.

Having known Chaubeys views for some time now especially that the origin of the R1a is far from settled I was not surprised to hear this. This in itself gives the lie to Josephs claims of the unambiguous conclusions of genetics about the hypothetical Aryan immigration.

Mitochondrial DNA vs Y-chromosomal DNA

Joseph claims that we only had mitochondrial (mt-) DNA (which is inherited from the mother) analysis till recently, which failed to capture the fact that it may have been mostly Aryan males who migrated first to the subcontinent and intermarried with the native women. This, apparently, has been conclusively established by a recent avalanche of Y-chromosomal DNA (which is inherited exclusively by sons from their fathers) data, which shows a Bronze Age gene flow into the subcontinent. This remark seems to suggest an embarrassing lack of familiarity with the literature.

Also, does Joseph seriously imagine geneticists would not have envisaged the possibility of males spearheading a migration all along? The first suggestion that Y-chromosomal DNA analysis may be making a case for Indo-European immigration, and the proposal that the R1a haplogroup (M17) may be a marker for this migration, was made as early as 2001.

This was subsequently contradicted in 2006 in a seminal Y-chromosomal DNA study by a group that included Richard Villems, Toomas Kivisild and Mait Metspalu, also of the Estonian Biocentre, and among the leading authorities in this area (Kivisild has since moved to Cambridge, but Villems and Metspalu are Chaubeys current colleagues at Tartu). Villems and Kivisild were, in fact, co-authors in the 2001 paper I just mentioned, but revised their view about a migration after a fresh analysis of more extensive data.

This paper, concluded, It is not necessary, based on the current evidence, to look beyond South Asia for the origins of the paternal heritage of the majority of Indians at the time of the onset of settled agriculture. The perennial concept of people, language, and agriculture arriving to India together through the northwest corridor does not hold up to close scrutiny. Recent claims for a linkage of haplogroups J2, L, R1a, and R2 with a contemporaneous origin for the majority of the Indian castes paternal lineages from outside the subcontinent are rejected...

The dominant narrative that Joseph talks about actually stems from this study, and Im not sure he is qualified to dismiss it as a bit of a stretch. This study, which has never really been contradicted, is, in fact, published in a much more respected journal than BMC Evolutionary Biology from where Joseph cites Martin Richards paper. This is significant, as good studies in this area have generally found a place in highly-ranked journals, even if they have arrived at diverging conclusions.

Indeed, this itself would suggest there are very eminent geneticists who do not regard it as settled that the R1a may have entered the subcontinent from outside. Chaubey himself is one such, and is not very pleased that Joseph has not accurately presented the divergent views of scholars on the question, choosing, instead to present it as done and dusted.

The R1a haplogroup

There are some inherent issues in regarding the R1a as a marker for any hypothetical Indo-European migration.

Firstly, Iranian populations, who are also speakers of the Indo-Iranian family of languages like most North Indians, have very little R1a. Also, tribal groups like the Chenchus of Andhra Pradesh and the Saharias of Madhya Pradesh show anomalously high proportions of R1a. The Chenchus speak a Dravidian language, and the Saharias an Austro-Asiatic one (though they have recently adopted Indo-European languages).

They are hunter-gatherer peoples who remained stunningly isolated without admixing much with other population groups, and consequently, their lifestyles have remained startlingly unchanged for millennia, as they would have been before the start of settled agriculture.

The best that studies which argued that the R1a could be used as a marker for the hypothetical Indo-European migration could do was to simply ignore these groups as aberrations. But is that very convincing? Note that it is possible no, almost certainly the case there were many tribal communities with high proportions of R1a that, unlike the Chenchus and Saharias, were assimilated into the caste matrix over the millennia. So how correct is it to link the R1a with an Indo-European migration?

Significantly, Richards et al acknowledge Chaubeys critical advice with their manuscript. That seems like a euphemism for saying that Chaubey (and, by extension, the Tartu school) had reservations about their conclusions, which is probably why he is not a co-author. So what should one make of Josephs claim that geneticists have converged on an answer?

If Underhill expressly stated to Joseph that he has now reversed his published position that there has been no significant genetic influx to Asia from Europe, indeed specifically that he is now convinced the R1a entered the subcontinent from outside, Joseph bafflingly does not reproduce this statement in his article.

The statement Joseph actually quotes merely points out that we have better data now, but that is not the same thing. Joseph also cites his 2015 paper, in which Chaubey is a co-author, but this paper actually underscores the limits of current technology, and says their data is too preliminary to jump to conclusions about migrations and culture shifts.

The genetic data at present resolution shows that the R1a branch present in India is a cousin clade of branches present in Europe, Central Asia, Middle East and the Caucasus; it had a common ancestry with these regions which is more than 6000 years old, but to argue that the Indian R1a branch has resulted from a migration from Central Asia, it should be derived from the Central Asian branch, which is not the case, as Chaubey pointed out.

In other words, contrary to what Joseph claims, as the Y-chromosomal DNA data stands today, there is no support for a recent migration into the subcontinent.

Ancestral North Indians (ANI) and Ancestral South Indians (ASI)

Joseph continues to tilt at windmills when talking about the ANI / ASI construct of David Reich et al., who used analysis autosomal DNA, which is different from mt- and Y-chromosomal DNA.

Joseph writes, ...this theoretical structure was stretched beyond reason and was used to argue that these two groups came to India tens of thousands of years ago, long before the migration of Indo-European language speakers that is supposed to have happened only about 4,000 to 3,500 years ago.

One doesnt know what to make of this. It was geneticists including Lalji Singh and K Thangaraj who were Reichs co-authors in the paper which proposed the ANI/ASI construct who argued that the ANI and ASI are considerably more than 12,500 years old, and not the result of any recent migration.

He then goes on to quote David Reich arguing in favour of a migration from the Steppe around 2500 BCE. Once again, Joseph presents this view as the last word on the subject, although not all geneticists agree.

For instance, Partha Majumdar and co-workers have very recently come up with quite different conclusions in the journal, Human Genetics: In contrast to the more ancient ancestry in the South than in the North that has been claimed, we detected very similar coalescence times within Northern and Southern non-tribal Indian populations. A closest neighbour analysis in the phylogeny showed that Indian populations have an affinity towards Southern European populations and that the time of divergence from these populations substantially predated the Indo-European migration into India, probably reflecting ancient shared ancestry rather than the Indo-European migration, which had little effect on Indian male lineages (emphasis mine).

The Evidence From Archaeology

Since Joseph believed he was shocking those who believed genetic analysis had disproved Aryan immigration theories, I shall return the favour.

Hypotheses of migrations of Bronze Age populations into the subcontinent fall afoul of archaeological evidence. Paradoxically, as I have described earlier, bronze itself goes missing from the archaeological record for several centuries that are supposed to correspond to the settling of the Bronze Age Indo-Europeans into the subcontinent. As one of the foremost authorities in the archaeology of the Indus Valley Civilisation, Professor Jonathan Mark Kenoyer of the University of Wisconsin points out, this actually reflects a prolonged lack of contact of the subcontinent with the regions the Aryans are supposed to have entered from.

Also, geological evidence shows that the Ghaggar-Hakra river, along whose channels numerous Harappan sites have been discovered, was the River Saraswati described in the Vedas and other ancient literature; indeed, the team of geologists led by Peter D Clift which carried out the geological studies asserted that the descriptions of the Saraswati in those texts was remarkably accurate, as I wrote in an earlier article.

Such findings negate the Aryan immigration model, establish the overlap (if not identity) of the Indus Valley and Vedic cultures, and push back the dates for the composition of the Vedic and other literature considerably.

Agriculture In Subcontinent Indigenous, Autochthonous

There is clear evidence of continuous inhabitation of the Gangetic plain from the Pleistocene. It is also abundantly clear that agriculture was developed indigenously, autochthonously, based on exploiting local resources, at multiple centres on the subcontinent the Saraswati-Indus region, the Gangetic plain, Eastern, Central and Peninsular India in a natural progression from a hunting-gathering lifestyle to a sedentary one, with no external stimulus, but with strong interaction between various regions of the subcontinent themselves right from the earliest Neolithic.

The myth that the founding of agriculture, whether in the Indus Valley or elsewhere in the subcontinent, is owed to migrations from West Asia (the so-called Fertile Crescent) is not supported by archaeological evidence.

Based on current evidence, whether genetic or archaeological, Josephs conclusion that, ...we are a multi-source civilization, not a single-source one, drawing its cultural impulses, its tradition and practices from a variety of lineages and migration histories, is quite simply totally wrong.

One cannot impressed by Josephs quoting of a blogger with a very questionable history like Razib Khan, while selectively omitting the comments of a known scholar in the area like Dr Gyaneshwer Chaubey after having sought them himself.

Can one be sure he has not interviewed other scholars, but left out their views from his article as they didnt suit his pre-determined agenda or just didnt interview scholars he felt held such views?

Joseph and others like him are welcome to write on any topic they please, and are even free to take sides in line with their prejudices. Indeed, all he has done is to paint a very recent paper in a not particularly highly-ranked journal as the final word in the debate, while coolly ignoring well-regarded studies which arrive at differing conclusions in significantly higher-ranked journals.

All one asks is, when writing on a much-debated topic like this one, they should at least show the intellectual sincerity to mention divergent points of view, and not try to create a false impression for the lay reader that they have been conclusively addressed. That is neither very honest nor commendable.

Here is the original post:
Genetics Might Be Settling The Aryan Migration Debate, But Not How Left-Liberals Believe - Swarajya

Nazneen Rahman at the day job: head of genetics, Institute of Cancer Research and the Royal Marsden Hospital. Photograph: Wellcome

Ive had an exciting and unusual few weeks. My group published a scientific paper revealing a new genetic cause of a childhood kidney cancer called Wilms tumour. This discovery has been of immediate benefit to families, providing an explanation for why their child got cancer, and information about cancer risks for other family members. During the same period, I also released my second album of original songs, called Answers No Questions. On one day, I found myself singing live on Radio London in the morning and talking genetics to the World Service in the evening.

Over the past few weeks, I have found it increasingly difficult to know quite how to answer the ubiquitous question what do you do?

For most of my adult life, I have replied: Im a scientist and a doctor. It is an accurate description. I am professor of human genetics at the Institute of Cancer Research, London, and head of cancer genetics at the Royal Marsden Hospital. For 20 years, my work has focused on identifying gene mutations that predispose us to getting cancer and then using that information to help patients and their families.

But I am also a singer-songwriter. This is a smaller activity than my science, but far more than hobby. I release music that people pay good money to experience.

As my music has become better known, more and more people have asked me about my unusual career combination. Dubiously, admiringly, wistfully, jealously, but most often simply because they are intrigued by the motivations and the practicalities.

This has forced me to consider how, if at all, these parts of my life are related. At first, I was adamant they were distinct facets of my character. I railed against modern societys pervasive need to simplify and pigeon-hole the human spirit. Most people have multiple passions and drivers. I am fascinated by these subterranean pursuits. One of the joys of sharing my previously secret musical existence (its not been all joy but thats another column) is that many scientists now share their secret passions with me pot throwing, flugel playing, novelty cakemaking, fire eating scientists are as wondrously idiosyncratic in their appetites as the rest of society.

I also rail against the cliche that people are drawn to science and music because they both have a mathematical basis. It may be true for some, but it has no relevance to my passion for music. I was singing complex harmonies to pop songs long before I learned the theory of music. I am an intuitive, emotional, spontaneous songwriter with little idea of the key, notes or time I am composing in until I have to write it down. There is little science in my music, but I have come to believe there may be music in my science. There is a kinship in how I do science and how I make music that flouts the division of science and the arts that our education system promotes.

My branch of science is genetics. Genetics is underpinned by a simple four-letter DNA code (designated by A, C, G, T). This code dictates how our bodies work. And how they can fail. This beautiful code is framed, shaped, constrained and enhanced by a multitudinous orchestra of associates that determine when, how, where, how long and how strong different parts of the code are played in each of our 30tn cells. DNA is also extraordinary in being able to copy itself with unbelievable accuracy while retaining the ability to mutate and evolve. The sophisticated controls and balances are breathtaking in their elegance. Our recent childhood cancer gene discovery revealed some insights into these control mechanisms and how cancer can occur if they go wrong. Studying genetics provides an endless variety of patterns to unravel, problems to solve, questions to answer. Gratifyingly, it also provides endless opportunities to bring benefits to humanity. In a hundred lifetimes I would not run out of genetic questions that excite me.

Music is underpinned by a simple 12-letter note code (designated by C, C#, D, D#, E, F, F#, G, G#, A, A#, B). These notes can be layered in almost infinite ways to produce music. In a hundred lifetimes I would not run out of music to write. My challenge has never been about finding the time to write songs, it has always been about finding the time to not lose songs. Snippets of music and lyrics are my constant companions. Most disappear into the clouds like lost balloons. But every now and again, I reach up, grab a string and tie one down, just before it is lost for ever.

Science and music make me feel like Im swimming in infinity pools of possibility, but within structures that keep me from drowning. The potential and expectation to keep delivering new things can be daunting to scientists and artists. The DNA code in genetics and the note code in music are my lifelines. They let me be audacious and unfettered. They give me confidence to dive in, even when I cant see the shore on the other side.

And the practicalities of delivering science and music are quite similar for me. Science is typically funded as three- to five-year projects. For example, I am currently leading a 4m collaborative programme, called the Transforming Genetic Medicine Initiative, which is building the knowledge base, tools and processes needed to deliver genetic medicine. To get science funding, you need to present, in great detail, a persuasive, innovative concept that seems worthwhile and feasible. But once you receive the funding there is considerable creative licence to alter the project, within the overall concept, because science is fast moving. You cannot predict everything you will do at the cutting-edge of knowledge, five years in advance.

My albums have also had three-year lifespans, though I didnt plan it that way. I dont plan them at all. My songs tend to be stories about the complexities of everyday life, inspired by words, subjects or images that briefly, randomly, ensnare me. I dont know what the songs will be about before I write them. There is no overall concept for the albums, at least not consciously. And yet I see now that each album had a central theme that wasnt apparent to me when I was writing them. Cant Clip My Wings, which I released in 2014, includes songs about how we adapt to loss. Lost loves, lost lives, lost dreams. My new album, Answers No Questions, includes songs about choice the complexities, burdens, excitement, pain and joys of making choices.

As I am writing this, I wonder if I am forcing these connections, if they are a post-hoc construct that allows me to give a more pleasing answer to why I am both scientist and songwriter. But I have truly come to believe that, in me, science and music are different manifestations of the same need. A central deep desire to create new things elegant, beautiful, new things. It doesnt much matter if its a scientific discovery, a clinic protocol that makes things easier for patients or a song that tells a human story from a fresh perspective. When it works it feels amazing. Even when it doesnt work, the journey is always paved with nuggets of enlightenment that feed into future creations.

So what do I do?

I think, at my core, I am a creative, though it would be perplexing to many if I started to describe myself this way. Science and music are the mediums in which I happen to create, undoubtedly an unusual combination. But maybe only because we are relentlessly conditioned, from an early age, to believe we must choose whether we are in the science or the arts camp. People from the arts camp routinely tell me they were hopeless at science, sometimes apologetically, sometimes as a badge of honour, a mark of their creativity. Likewise, scientists worry that any proficiency in creativity might be interpreted as a deficiency in objectivity, the bedrock of science. It seems our society has lapsed into considering activity in the sciences and the arts a zero-sum game. It is not.

What would happen if we stopped constraining ourselves and our children in this way? If we embraced and fostered fluid boundaries between the sciences and the arts? If many more people were able to cross freely in and out of both worlds, successfully and unapologetically?

I believe science, art, individuals and society would reap countless benefits.

Answers No Questions is out now; nazneenrahman.com

Read the original post:
Nazneen Rahman: 'Science and music are mediums in which I create' - The Guardian

JUNE 18, 2017

THERES A SCENE in Antoine de Saint-Exuprys The Little Prince where the alien prince, fallen to Earth, comes across a fox. Come and play with me, he proposes to the fox, who replies, I cant play with you. Im not tamed. The prince, whos never heard the word tamed before, asks what it means. Its something thats too often neglected, the fox tells him. It means, to create ties. [] If you tame me, well need each other. Youll be the only boy in the world for me. Ill be the only fox in the world for you. [] [I]f you tame me, it will be as if the sun came to shine on my life. I shall know the sound of a step that will be different from all the others.

In 1952, nine years after Saint-Exuprys book was published, the Russian geneticist Dmitri Belyaev set out, like the Little Prince, to tame a fox or rather, foxes. His goal was to better understand how domesticated dogs evolved from the wolf, and he proposed to do this by domesticating the silver fox, the wolfs genetic cousin. By mimicking the wolfs transformation with a close relative, Belyaev thought, we could better understand one of the great mysteries of prehistory: the dogs route to domestication.

We know more about this process now than we did when Belyaev embarked on his research project decades ago. To his scientific peers, Belyaevs belief that he could replicate 10,000 years of evolution and breeding in a few decades with a species that had never been domesticated before, seemed entirely fanciful. But he turned out to be right: within a few years of starting his experiment, the foxes were already showing signs of domestication; within decades, they were on their way to becoming their own species. How to Tame a Fox (And Build a Dog) traces the history of Belyaevs experiment against the background of first the Soviet Union and then postCold War Russia. Its co-authored by the geneticist Lyudmila Trut, who joined Belyaevs team early on and has been the lead researcher of the fox domestication project since 1959, and the evolutionary biologist Lee Alan Dugatkin.

Domesticated animals exist in a peculiar gray area between the world of humanity and the rest of nature. From the Book of Genesis to the modern environmental movement, we tend to understand nature as something that we stand apart from and exert power over, whether to dominate or to protect. But cats, dogs, horses, and other domesticated creatures exist in a liminal space between these two worlds. As W. G. Sebald says of the dog, His left (domesticated) eye is attentively fixed on us; the right (wild) one has a little less light, strikes us as averted and alien.

Domestication is not simply the engineering of a change in animal behavior; it is a matter, as Dugatkin and Trut write in their opening pages, of constructing a brand new biological creature. Dogs, after all, are a separate species from wolves, and housecats are so different from their feline cousins that its not entirely clear from which species they were domesticated (though most biologists agree that it was probably the Middle Eastern wildcat). Domestication is not just a question of selectively breeding some traits at the expense of others; its about fundamentally changing the animal.

Across species, domesticated animals seem to share a number of traits that differentiate them from their wild counterparts. Most have shorter faces and curly and floppy tails, traits associated with delayed physiological development and remaining in a stage of perpetual adolescence; biologists refer to this as neoteny. Domestic animals also tend to develop different coloration patterns, and unlike their wild cousins, who mate only once a year, theyre fertile year round. Other traits are significant but harder to measure: a dog may not have the same apparent aptitude for solving puzzles as a wolf, but will display more social intelligence in its ability to manipulate human emotions.

The riddle of domestication has always been how to unravel this ball of traits, and learn how they came to be associated with one another. Were early domestic animals selected for their usefulness to humans (cats for pest control, dogs for security and hunting), and then socialized from there? Were their neotenic traits necessary for their domestication, as animals that remained juveniles were perhaps easier to train? Was the wolfs nature as a pack animal, and responsiveness to socialization and group identity, crucial to its taming? And what of the superficial aesthetic differences do they have any bearing on domestication? Farmers raising cows, after all, had nothing to gain from their cows having black-and-white spotted hides, Dugatkin and Trut note. Why would pig farmers have cared whether their pigs had curly tails?

Belyaevs hypothesis was that the single most important defining trait was comfort around human beings. Zebra and deer, for example, share many traits in common with horses but have long resisted any attempts at domestication. Zebra, under constant threat from predators, have developed a fierce defensiveness, whereas deer remain skittish and are universally nervous around humans. What separates both of these animals from their close genetic cousin the horse is the latters tolerance of humans. Early attempts to domesticate horses, DNA evidence suggests, were based on selecting for agreeableness and manipulating the horses innate fear response.

Among the numerous traits that identify domestic animals, then, Belyaev used as his sole criterion tolerance for human beings. Foxes tend to be either aggressive or skittish around humans; Belyaev and his team focused on those that seemed least defensive. These were bred together, and successive generations were likewise measured for their tolerance for humans, with the researchers hoping that eventually this quality could be bred in offspring.

Within three breeding seasons, the researchers were seeing results: Some of the pups of the foxes theyd selected were a little calmer than their parents, grandparents, and great-grandparents, Trut and Dugatkin write. They would still sneer and react aggressively sometimes when their keepers approached them, but at other times they seemed almost indifferent. Even more surprising, though, was how quickly these behavioral changes were accompanied by other differences. In a matter of years, hormones associated with stress decreased, while levels of serotonin (which decreases anxiety and elevates ones mood) increased. The foxes went from being merely indifferent around the researchers to actively soliciting their affection. Eventually, their tails would even wag at the sight of humans something no other animal besides a dog has been known to do.

Selecting for tameness also led to a series of physical changes: Belyaevs foxes had bushier tails, shorter faces, lighter fur. Which is to say: Traits that were not in any way selected for nonetheless began to assert themselves. At one point, the foxes began making a sound that at first confounded Trut and her team, until she realized that they appeared to be mimicking human laughter. As they ultimately concluded, the tame foxes were making this noise in order to attract human attention and prolong interaction with people. They were displaying the same kind of social intelligence that dogs do when they perform tricks for their masters.

The fox experiment bore out Belyaevs initial hypothesis about tolerance for humans as the key to domestication. These results suggest that many of the various other traits associated with domestication are in fact already latent in animals genetic codes; its just that, in the wild, these traits are inactive, rarely expressing themselves. Selective breeding can allow them to come to the fore relatively quickly. Shake up the fox genome by placing foxes in a new world where calm behavior toward humans is the ultimate currency, Dugatkin and Trut conclude, and youll get lots of other changes mottled fur, curly, wagging tails, and better social cognition as well.

The story of Belyaev and Truts decades-long experiment is fascinating, though in How to Tame a Foxs telling some important details get left out. In crafting a heartwarming story of how easy it was to create docile, loving pets, Dugatkin and Trut dont dwell on the fact that they were also trying to create exceptionally aggressive foxes to further test the hypothesis. Nor were they just breeding foxes: other species, including rats and beavers, were also bred for both aggressiveness and tameness. According to one anecdotal report of the project that isnt mentioned in the book, Soviet officials had planned to use the most aggressive beavers as a line of defense against a possible US invasion. One wonders what other strange tidbits might have come to light had the authors not chosen to selectively shape their narrative. As a result, the book itself feels much like its subjects: bred for tameness.

It might have been better had How to Tame a Fox not been co-written by one of the principal researchers, so as to introduce a modicum of objectivity and critical distance into the writing. At times the book reads like a third-person memoir: Pushinka [one of the foxes] lay by Lyudmilas feet while she worked at her desk, and she loved for Lyudmila to play with her and take her for walks around the area. A favorite game was when Lyudmila would hide a treat in her pocket and Pushinka would try to snatch it out. Such passages are often lovely and do help to convey the remarkable level of domestication the foxes had achieved in such a small span of years (and only the coldest hearted wont melt at the photos of the foxes themselves). But in a book that largely skimps on the scientific and philosophical implications of its narrative, they can feel a bit too sentimental. It is also odd to read passages that describe Trut as a woman of great warmth and an unassuming demeanor, whose formidable energy and determination made her a force to be reckoned with when she is also listed as a co-author of the book.

One thing How to Tame a Fox does reveal is the precariousness inherent in government-funded research, with lessons that go far beyond Soviet Russia. In the early 50s, when Belyaev began his project, the entire field of genetics was under assault in the USSR. A well-placed friend of Stalin, Trofim Lysenko, had promised that he could increase crop yields by freezing seeds before planting. Lysenkos claim was not only false, it ran counter to the prevailing understanding of crop genetics. Since Lysenko knew geneticists could unmask him as a fraud, he began a campaign to discredit the entire discipline, labeling them as saboteurs. Thus, when Belyaev first described his research program to Trut, he told her it could not appear to have anything to do with genetics; instead, it had to be described as an inquiry into fox physiology.

After Stalins death, Lysenkos stranglehold on the discipline loosened, and geneticists could once again work without fear of reprisal. But with the fall of the Soviet Union and the economic crash of the 1990s, research budgets were slashed, and the project nearly ended for lack of funds. Trut took to begging passersby for food to feed her starving animals; eventually she was forced to sell some of the domestic foxes for pets, and some in the control groups for fur. Only an internationally published paper on her results saved the project, triggering a fundraising campaign that kept the animals alive.

Belyaev died in 1986, but he had hoped to one day write a book himself, which he planned to call Man Is Making a New Friend. How to Tame a Fox (and Build a Dog) is not far off from what Belyaev envisioned: written for a general audience, it chronicles the story of a scientific gambit that was more successful that even its creators had dreamed. Its an inspiring reminder of how much we still dont know about the world, and how much can be learned by taking bold chances. Its also a cautionary tale about the risks of state-funded science that has nearly as much relevance to Trumps United States, where federal research budgets are in danger of being slashed right and left, as it does to Stalins Russia.

But Belyaevs experiment didnt just produce new knowledge; it also created a new species of animal, one thats become entirely dependent on humans, and its worth asking what the ethical and philosophical consequences of this might be. Some scientists believe that wolves actively participated in their own domestication; thousands of years ago, certain wolves may have made the calculation that, by sucking up to humans, they could live an easier life. These wolves gave up autonomy and freedom in exchange for food, shelter, and protection. The gamble ultimately paid off: there are now only about three hundred thousand wolves in the wild, and over half a billion dogs.

But a dogs life is not an easy one, especially without a human being to care for it. Many contemporary breeds lack the skills to fend for themselves, having depended on their masters for generations. Perhaps in the future wild foxes will go extinct, and the only foxes that remain will be the domesticated ones, the ones that have endeared themselves to humans to such a degree that even in times of strife and scarcity we will look out for them. But the precarious state of Belyaevs project may well signal another outcome, one in which these foxes, whove thrown their all in with their human protectors, may find a darker fate awaiting them. If the money to keep the program going dries up, and theres no market for them as pets, what then? In The Little Prince, Saint-Exuprys protagonist does indeed tame his new friend, but before he does the fox offers this warning: People have forgotten this truth. But you mustnt forget it. You become responsible for what youve tamed.

Colin Dickey is the author, most recently, of Ghostland: An American History in Haunted Places.

Follow this link:
Making New Friends: The Genetics of Animal Domestication - lareviewofbooks

PIERRE South Dakotas Research and Commercialization Council (RCC) has selected four research centers to receive funding through the Governors Research Center Program.

At its meeting last month, the RCC chose the following new centers for funding:

South Dakota Center for Biologics Research & Commercialization, led by Dr. Christopher-Hennings at South Dakota State University, will receive $3,817,603 over five years to conduct translational research in nutraceuticals, probiotics, vaccines and diagnostic collaboration with industry partners, who will license and commercialize the technologies developed by the center. The centers overarching goal is to become a nationally recognized center of excellence in biologics research.

Center for Fluorinated Functional Materials, led by Dr. Sun at the University of South Dakota, will receive $2,710,969 over five years to build a self-sustaining discovery-based research center to commercialize fluorinated functional materials in the sectors of materials and advanced manufacturing, energy and environment and human health and nutrition.

Center for Genetics & Behavioral Health, led by Dr. Forster at the University of South Dakota, in collaboration with the Avera Institute for Human Genetics, will receive $3,466,300 over five years to study genetic and environmental influences that interact with other biological, psychological and behavioral factors to impact post-traumatic stress disorder (PTSD). The center aims to place South Dakota at the forefront of personalized treatment of trauma-related illness to significantly reduce the substantial health, financial and personal burden of PTSD and associated disorders.

Composite and Nanocomposite Advanced Manufacturing/Biomaterials Center, led by Dr. Salem at the South Dakota School of Mines & Technology, will receive $1,806,427 over five years to develop low-cost biopolymers from renewable sources and develop commercially-viable processes for the transformation of these materials into valuable polymers and high performance bio-composites and bio-nanocomposites.

The goal of the Governors Research Center Program is threefold: to develop focused research centers that are competitive for external research funding; to develop and license inventions; and to support existing and spin off start-up companies in South Dakota, said Nathan Lukkes, assistant vice president for research and economic development at the South Dakota Board of Regents.

Since its inception in 2005, the states investment in this program has generated more than $249 million in additional extramural research funding, in excess of 150 invention disclosures, and provided research opportunities for over 940 students, Lukkes said. Additionally, the program has spun out or attracted more than 20 startup companies, which currently employ over 185 people in South Dakota and include such companies as Alumend, SBS CyberSecurity and VRC Metal Systems, to name a few.

The RCC, which is comprised of five public members appointed by the Governor and four members serving by virtue of their position, is charged with oversight and selection of the research centers. The Governors Office of Economic Development and the Board of Regents jointly administer the Governors Research Center Program.

Read more:
State Research Centers To Receive State Funding - Yankton Daily Press

The Hindu

How genetics is settling the Aryan migration debate The Hindu The dating of the profound population mixture event that Reich refers to was arrived at in a paper that was published in the American Journal of Human Genetics in 2013, and was lead authored by Priya Moorjani of the Harvard Medical School, and ...

See more here:
How genetics is settling the Aryan migration debate - The Hindu

Scientists have discovered a new cellular pathway that can promote and support the growth of cancer cells. In a mouse model of melanoma, blocking this pathway resulted in reduction of tumor growth. The study, which appears in Science, offers a novel opportunity to develop drugs that could potentially inhibit this pathway in human cancer cells and help control their growth.

We had been studying components of this pathway for several years, said senior author Dr. Andrea Ballabio, professor of molecular and human genetics at Baylor College of Medicine and Texas Childrens Hospital in Houston, Texas, and director of the Telethon Institute of Genetics and Medicine in Naples, Italy. We know that the pathway is important for normal cells to carry their activities as it is involved in regulating metabolism, that is, how cells process nutrients to obtain energy and how cells use energy to grow. In this study we wanted to learn more about how the pathway regulates its activity.

Pathways involved in cellular metabolism typically regulate themselves, meaning that some components of the pathway control each others activities. We suspected that the pathway was autoregulated, and we confirmed it in this study. Our experimental approaches showed that there is a feedback loop within the path that allows it to control itself.

An important pathway for normal cellular activities

Ballabio and his colleagues studied the role of the pathway in two normal cellular activities; how cells respond to physical exercise and how they respond to nutrient availability. In terms of physical exercise, the researchers determined that the self-regulating mechanism they discovered is essential for the body builder effect.

Some athletes take the aminoacid leucine or a mixture of aminoacids immediately after exercising, which promotes protein synthesis that leads to muscle growth. This is the body builder effect, Ballabio said. When we genetically engineered mice to lack the pathway, we lost the body builder effect.

The researchers had a group of normal mice and another of mice lacking the pathway. Both groups were set to exercise and fed leucine immediately after. While normal mice showed enhanced protein synthesis, the mice without the pathway did not.

In healthy organisms, this pathway also allows cells to adapt more efficiently to nutrient availability, Ballabio said. For example, when transitioning from a period of starvation to one in which food is available, cells need to switch from catabolism to anabolism. Starvation promotes catabolism the breakdown of nutrients to obtain energy to function and eating promotes anabolism the buildup of molecules, such as proteins. The feedback we discovered mediates the switch from catabolism to anabolism, allowing organisms to adapt to food availability.

An important pathway for cancer growth

The scientists also studied the role this pathway might play in cancer cells. They discovered that overactivation of this pathway, which is observed in some types of cancer such as renal cell carcinoma, melanoma and pancreatic cancer, is important to promote and support the growth of cancer cells in culture and animal models.

Most importantly, we demonstrated in our study that blocking the pathway resulted in reduction of tumor growth in an experimental model of human melanoma transplanted into mice, Ballabio said. I am most excited about the future potential therapeutic applications of this discovery against cancer. Developing pharmacological treatments that interfere with this pathway might one day help stop tumor growth.

Rare disease discoveries can improve our understanding of common diseases

Our lab focuses on rare genetic diseases, such as lysosomal storage genetic disorders, in which we originally studied this pathway, Ballabio said. Then, we discovered that the pathway is also important in cancer. Our and other researchers work on rare genetic diseases sometimes produces findings that can potentially be applicable to more common diseases, such as cancer.

For a complete list of the authors of this work and their affiliations, please refer to the published article.

This study was supported by grants from the Italian Telethon Foundation (TGM11CB6); European Research Council Advanced Investigator grant no. 250154 (CLEAR) and no. 341131 (InMec); U.S. National Institutes of Health (R01-NS078072); and the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) IG 2015 Id 17639 and IG 2015 Id 17717.

Read more:
Newly revealed cellular pathway may lead to cancer therapies - Baylor College of Medicine News (press release)

Slowing down the aging process might be possible one day with supplements derived from gut bacteria. Scientists at Baylor College of Medicine and the University of Texas Health Science Center at Houston have identified bacterial genes and compounds that extend the life of and also slow down the progression of tumors and the accumulation of amyloid-beta, a compound associated with Alzheimers disease, in the laboratory worm C. elegans. The study appears in the journal Cell.

The scientific community is increasingly aware that our bodys interactions with the millions of microbes in our bodies, the microbiome, can influence many of our functions, such as cognitive and metabolic activities and aging, said corresponding author Dr. Meng Wang, associate professor of molecular and human genetics at Baylor and the Huffington Center On Aging. In this work we investigated whether the genetic composition of the microbiome might also be important for longevity.

This question is difficult to explore in mammals due to technical challenges, so the researchers turned to the laboratory worm C. elegans, a transparent, simple organism that is as long as a pinhead and shares essential characteristics with human biology. During its 2 to 3 week long lifespan, the worm feeds on bacteria, develops into an adult, reproduces, and progressively ages, loses strength and health and dies. Many research laboratories around the world, including the Wang lab, work with C. elegans to learn about basic biological processes.

We think that C. elegans is a wonderful system in which to study the connection between bacterial genes and aging because we can very fine tune the genetics of microbes and test many genes in the worm in a relatively short time, Wang said.

Testing thousands of genes, one at a time.

To study the effect of individual bacterial genes on the lifespan of C. elegans, Wang joined efforts with Dr. Christophe Herman, associate professor of molecular and human genetics and molecular virology and microbiology at Baylor, and other colleagues who are experts in bacterial genetics. They employed a complete gene-deletion library of bacterium E. coli; a collection of E. coli, each lacking one of close to 4,000 genes.

We fed C. elegans each individual mutant bacteria and then looked at the worms life span, Wang said. Of the nearly 4,000 bacterial genes we tested, 29, when deleted, increased the worms lifespan. Twelve of these bacterial mutants also protected the worms from tumor growth and accumulation of amyloid-beta, a characteristic of Alzheimers disease in humans.

Further experiments showed that some of the bacterial mutants increased longevity by acting on some of the worms known processes linked to aging. Other mutants encouraged longevity by over-producing the polysaccharide colanic acid. When the scientists provided purified colanic acid to C. elegans, the worms also lived longer. Colanic acid also showed similar effects in the laboratory fruit fly and in mammalian cells cultured in the lab.

The researchers propose that, based on these results, it might be possible in the future to design preparations of bacteria or their compounds that could help slow down the aging process.

Colanic acid mediates crosstalk between bacteria and mitochondria

Interestingly, the scientists found that colanic acid regulates the fusion-fission dynamics of mitochondria, the structures that provide the energy for the cells functions.

These findings are also interesting and have implications from the biological point of view in the way we understand host-microbe communication, Wang said. Mitochondria seem to have evolved from bacteria that millions of years ago entered primitive cells. Our finding suggests that products from bacteria today can still chime in the communication between mitochondria in our cells. We think that this type of communication is very important and here we have provided the first evidence of this. Fully understanding microbe-mitochondria communication can help us understand at a deeper level the interactions between microbes and their hosts.

Other contributors to this work include Bing Han, Priya Sivaramakrishnan, Chih-Chun J. Lin, Isaiah A.A. Neve, Jingquan He, Li Wei Rachel Tay, Jessica N. Sowa, Antons Sizovs, Guangwei Du and Jin Wang.

Financial support for this project was provided by the National Institutes of Health grants R01AG045183, R01AT009050, DP1DK113644, R01HL119478, R01GM088653, R01GM115622, R01CA207701 and Howard Hughes Medical Institute Faculty Scholar Award.

See the original post:
Gut bacteria might one day help slow down aging process - Baylor College of Medicine News (press release)