Category Archives: Transhuman News

Users pay 100 to the Silicon Valley company 23andme for a breakdown of their ancestryALAMY

The ancestry company 23andme has become the worlds first genetics testing firm to create a drug created from its customers DNA samples.

The Silicon Valley company has developed and sold a drug designed to treat inflammatory diseases such as psoriasis. It is based on its database of around 10 million DNA samples it has collected since it was founded in 2006.

23andme has sold the rights to the drug to the Spanish pharmaceutical company Almirall for an undisclosed sum.

The companys chief executive is Anne Wojcicki, whose sister, Susan, is the chief executive of YouTube and whose ex-husband Sergey Brin is the co-founder of Google.

It is one of several genetics companies that offers home testing kits which allow people to get a breakdown of

Want to read more?

Subscribe now and get unlimited digital access on web and our smartphone and tablet apps, free for your first month.

Read this article:
Genetic testing firm 23andMe is first to create a drug using its customers' DNA - The Times

11-year-old Bertrand Might (center) surrounded by his family, including his father, Matt Might (second from right), and his mother, Cristina Might (second from left). Credit: The Might family

Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that cells from children with NGLY1 deficiency a rare disorder first described in 2012 lack sufficient water channel proteins called aquaporins. The discovery was published in Cell Reports and may help explain the disorders wide-ranging symptoms including the inability to produce tears, seizures and developmental delays and opens new avenues to find therapies to treat the disorder.

Our findings uncover a new and completely unexpected job for NGLY1, which was originally thought to only cleave sugars from proteins, says Hudson Freeze, Ph.D., director, and professor of the Human Genetics Program at Sanford Burnham Prebys and senior author of the study. This new information, which includes the molecular signals NGLY1 uses to drive aquaporin production, fundamentally shifts how we approach drug development. Most immediately, we can begin to screen for existing FDA-approved drugs that may increase aquaporin levels.

Burst cells are shown in orange, and intact cells are shown in blue (the dye used stains the DNA in a nucleus). Unlike normal cells (left), cells missing the NGLY1 protein (right) refused to split open when placed in distilled water. The cells pictured are from mice. Credit: Sanford Burnham Prebys

The first patient with NGLY1 deficiency, then-four-year-old Bertrand Might, was diagnosed in 2012. The condition occurs when both copies of the NGLY1 gene contain mutations. As a result, children with NGLY1 deficiency produce little or no N-glycanase1 a protein that removes sugars from proteins during the cells regular recycling process. Today, approximately 60 people in the world have been identified with NGLY1 deficiency. There is no cure, and existing treatments only address a few of the disorders symptoms.

This discovery is a giant leap forward in our understanding of NGLY1 deficiency and our ability to find a drug for the condition, says Matt Might, Ph.D., Bertrand Mights father and chief scientific officer of NGLY1.org, which funded the research. In addition to exploring new treatment avenues, we can immediately start to test currently available drugs to see if they may help Bertrand and other children living with NGLY1 deficiency.

Because of NGLY1s established role in helping recycle proteins, scientists predicted that cells that lack NGLY1 would fill with unrecycled proteins. However, despite numerous experiments by Freeze and others, this has not been observed.

Hudson Freeze, Ph.D., director and professor of the Human Genetics Program at Sanford Burnham Prebys and senior author of the study. Credit: Sanford Burnham Prebys

Mitali Tambe, Ph.D., a postdoctoral associate in the Freeze lab and the first author of the study, set out to shed light on this mystery when she made an unexpected discovery. While normal cells burst open when placed in distilled water, cells from children with an NGLY1 mutation refused to pop open.

At first I thought what every scientist initially thinks: I made a mistake, says Tambe. But this observation actually revealed a previously unknown role for NGLY1 protein.

The unexpected finding prompted the scientists to dig in deeper. In addition to studying skin cells from three children with NGLY1 deficiency, the researchers created human and obtained mouse cells that either lacked NGLY1 or produced excess amounts of the protein. In these studies, they found that cells that lacked the NGLY1 protein had fewer aquaporins proteins that connect the inside and outside of a cell and control water movement and were resistant to bursting open when placed in water. These results were reversed in cells that were given excess levels of NGLY1. The researchers also identified the molecular signals NGLY1 uses to instruct cells to produce aquaporins, proteins called Atf1 and Creb1, which may lead to useful drug targets.

In addition to regulating tear and saliva production, aquaporins are involved in many brain functions, such as cerebrospinal fluid production, explains Tambe. Lack of aquaporins may explain many of the symptoms seen in children who are NGLY1-deficient.

The scientists devised a clever experiment to determine if NGLY1 is regulating aquaporin levels through its expected sugar-removal function or in another manner. They created two cell types that either produced a normal NGLY1 protein or NGLY1 with the sugar-cleaving area disabled. The altered protein successfully altered aquaporin levels indicating that NGLY1 has a second function in addition to its sugar-removing (enzymatic) activities.

Our study shows there is more to NGLY1 than its well-known function of removing sugars from proteins, says Freeze. Together, our findings open important new paths to understanding the pathogenesis of NGLY1 deficiency and ultimately finding treatments.

Reference: N-Glycanase 1 Transcriptionally Regulates Aquaporins Independent of Its Enzymatic Activity by Mitali A. Tambe, Bobby G. Ng and Hudson H. Freeze, 24 December 2019, Cell Reports.DOI: 10.1016/j.celrep.2019.11.097

Research reported in this article was supported by the Bertrand Might Research Fund and NGLY1.org. Additional study authors include Bobby Ng.

See the article here:
11 Year-Old Bertrand Might Cant Cry Scientists Have Now Discovered Why - SciTechDaily

Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that cells from children with NGLY1 deficiency--a rare disorder first described in 2012--lack sufficient water channel proteins called aquaporins. The discovery was published in Cell Reports and may help explain the disorder's wide-ranging symptoms--including the inability to produce tears, seizures and developmental delays--and opens new avenues to find therapies to treat the disorder.

"Our findings uncover a new and completely unexpected 'job' for NGLY1, which was originally thought to only cleave sugars from proteins," says Hudson Freeze, Ph.D., director and professor of the Human Genetics Program at Sanford Burnham Prebys and senior author of the study. "This new information, which includes the molecular signals NGLY1 uses to drive aquaporin production, fundamentally shifts how we approach drug development. Most immediately, we can begin to screen for existing FDA-approved drugs that may increase aquaporin levels."

The first patient with NGLY1 deficiency, then-four-year-old Bertrand Might, was diagnosed in 2012. The condition occurs when both copies of the NGLY1 gene contain mutations. As a result, children with NGLY1 deficiency produce little or no N-glycanase1--a protein that removes sugars from proteins during the cell's regular recycling process. Today, approximately 60 people in the world have been identified with NGLY1 deficiency. There is no cure, and existing treatments only address a few of the disorder's symptoms.

"This discovery is a giant leap forward in our understanding of NGLY1 deficiency and our ability to find a drug for the condition," says Matt Might, Ph.D., Bertrand Might's father and chief scientific officer of NGLY1.org, which funded the research. "In addition to exploring new treatment avenues, we can immediately start to test currently available drugs to see if they may help Bertrand and other children living with NGLY1 deficiency."

A surprise discovery unlocks new insights into NGLY1

Because of NGLY1's established role in helping recycle proteins, scientists predicted that cells that lack NGLY1 would fill with unrecycled proteins. However, despite numerous experiments by Freeze and others, this has not been observed.

Mitali Tambe, Ph.D., a postdoctoral associate in the Freeze lab and the first author of the study, set out to shed light on this mystery when she made an unexpected discovery. While normal cells burst open when placed in distilled water, cells from children with an NGLY1 mutation refused to pop open.

"At first I thought what every scientist initially thinks: I made a mistake," says Tambe. "But this observation actually revealed a previously unknown role for NGLY1 protein."

The unexpected finding prompted the scientists to dig in deeper. In addition to studying skin cells from three children with NGLY1 deficiency, the researchers created human and obtained mouse cells that either lacked NGLY1 or produced excess amounts of the protein. In these studies, they found that cells that lacked the NGLY1 protein had fewer aquaporins--proteins that connect the inside and outside of a cell and control water movement--and were resistant to bursting open when placed in water. These results were reversed in cells that were given excess levels of NGLY1. The researchers also identified the molecular signals NGLY1 uses to instruct cells to produce aquaporins, proteins called Atf1 and Creb1, which may lead to useful drug targets.

"In addition to regulating tear and saliva production, aquaporins are involved in many brain functions, such as cerebrospinal fluid production," explains Tambe. "Lack of aquaporins may explain many of the symptoms seen in children who are NGLY1-deficient."

The scientists devised a clever experiment to determine if NGLY1 is regulating aquaporin levels through its expected sugar-removal function or in another manner. They created two cell types that either produced a normal NGLY1 protein or NGLY1 with the sugar-cleaving area disabled. The altered protein successfully altered aquaporin levels--indicating that NGLY1 has a second function in addition to its sugar-removing (enzymatic) activities.

"Our study shows there is more to NGLY1 than its well-known function of removing sugars from proteins," says Freeze. "Together, our findings open important new paths to understanding the pathogenesis of NGLY1 deficiency and ultimately finding treatments."

Reference:Tambe, M. A., Ng, B. G., & Freeze, H. H. (2019). N-Glycanase 1 Transcriptionally Regulates Aquaporins Independent of Its Enzymatic Activity. Cell Reports, 29(13), 4620-4631.e4. https://doi.org/10.1016/j.celrep.2019.11.097

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.

Read more here:
Why Cant Bertrand Might Cry? Missing Water Channels Could Be the Answer - Technology Networks

In November 2018, Chinese biophysics researcher He Jiankuimade a historic announcement.

Two twin girls nicknamed Lulu and Nana had become the worlds first genetically modified human beings.

Using a gene-editing technology known as CRISPR, He had manipulated the DNA of the embryos that would become the girls in an effort to make them immune to the HIV virus.

What first seemed like a historic triumph of science, however, quickly became one of the most infamous scandals in medical history.

The researcher was swiftly fired from his university, put under police investigation, and denounced by experts around the world who said he jumped the gun and carried out an experiment that was unsafe and unethical.

In December, He was sentenced to three years in prison for illegally carrying out human embryo gene-editing intended for reproduction. Its unclear whether the experiment caused any genetic damage to Lulu and Nana or if they are even resistant to the HIV virus.

Kiran Musunuru, one of the worlds foremost genetics researchers, was the first expert to publically condemn Hes experiment.

Nonetheless, Musunuru says the birth of the Chinese twins marks the beginning of a new human era, the possibilities of which are boundless.

Potential future implications of gene-editing technology range from preventing genetic diseases to producing designer babies with custom traits to creating superhumans and controlling our own evolution.

With the release of his new book, The CRISPR Generation: The story of the Worls First Gene-Edited Babies, The Globe Posts Bryan Bowmanspoke to Musunuru about where this technology could go from here and what it could mean for the future of humanity.

The following interview is lightly condensed and edited for length and clarity.

Bowman: Could you explain what CRISPR is broadly and how that technology evolved to where it is today?

Musunuru: CRISPR is one type of gene-editing tool. Gene editing is a technology that allows us to make changes to genes in the DNA and in the cells in the body. If were talking about human beings, typically were talking about changes that are related to health or disease.

There are several types of gene editing tools, but CRISPR is by far the most popular one. CRISPR is interesting because it wasnt invented. It actually exists naturally in all sorts of bacteria. It evolved as a sort of an immune system that can fight off viral infections. Just like we can get viral infections, it turns out bacteria can get viral infections as well. And so bacteria created a system by which they can fight off viruses. So thats where CRISPR came from.

Over the past couple of decades, a variety of very talented scientists identified it, discovered it in bacteria, and then were able to adapt it into a gene-editing tool that can now be used in human cells.

What we can do with CRISPR is either turn off genes and thats easier to do or we can make more precise changes to genes such as correcting a mutation that causes disease.

Bowman: Last year, there was the famous or infamous case where Dr. He Jiankui in China covertly created the first gene-edited babies. And I understand that you were the first expert to publicly condemn the experiment. What exactly did Dr. He do and why did you feel it was so unethical?

Musunuru: What he was trying to do was use CRISPR to turn off a gene called CCR5. By turning off this gene, he was hoping to make the babies that were born resistant to HIV infection, HIV being the virus that causes AIDS.

There are many people who are naturally born with this chain turned off and theyre resistant to HIV. So the rationale was, well, Im going to try to create babies who have the same trait.

What he did was problematic for two reasons. One, it was, to put it lightly, a scientific disaster. Everything you worry about going badly with CRISPR actually did happen. Any technology has a potential for a lot of good with the potential for bad. I compare it to fire. It can be very useful. But if youre not careful, it can cause wildfires and a lot of damage and hurt a lot of people. Its the same with CRISPR. It can do a lot of good. It can help patients who have bad diseases. But if youre irresponsible with it, it could actually cause unintended genetic damage.

Its not clear whether these kids that were born they were twin girls nicknamed Lulu and Nana its not clear whether theyre actually protected against HIV infection. Its not clear whether they might have suffered some genetic damage that might have health consequences for them. Its not clear whether the genetic damage if it did occur could get passed down to their children and affect future generations.

So scientifically, there are a lot of problems with it. The work was very premature. I would say that if we were ever going to do this in a reasonable, rational, safe way, were years away from doing it. But he went ahead and just did it anyway. You can call him a rogue scientist, as clich as it is. And he did it in conditions of secrecy. There was essentially no oversight. And potentially these twins and future generations might suffer the consequences.

The other problem is a problem of ethics. The way in which he did it basically violated every principle of ethical medical research in the textbook. Basically, everything that you could do wrong, he did it wrong.

Whenever we do an experimental procedure, we hope that the benefits greatly outweigh the risks. What he was trying to do was protect these kids from HIV. But the truth is, they were in no particular danger of getting HIV compared to the average person. In China, the prevalence of HIV is about 0.1 percent. So there wasnt really much for them to gain. Even if they did somehow during their lifetime get the HIV infection, we have good treatments to prevent it from proceeding to full-blown AIDS.

So what was the benefit of doing this procedure? You have to balance that against the harms. And the genetic damage thats possible that raises risks of things like cancer and heart disease and other diseases. When you have those risks and very little benefit, then its just not a favorable ratio. And thats intrinsically unethical.

Bowman: Seeing as you said that were years away from doing something like this in a more responsible and ethical way, what are the greatest challenges to getting to a point where parents will have the option to go forth with a gene-editing procedure that might prevent their children from suffering from some kind of genetic disease?

Musunuru: There are really two aspects to this. One is a scientific or medical aspect. Can we get to a place where gene-editing of embryos is well-controlled? Where we know that what were doing is truly safe and appropriate from that perspective?

The second issue is really a decision more for broader society. Is this something that we should be doing, something we want to be doing? This is less about the science and more about ethics and morality and legality and religious values and all sorts of other things. Reasonable people can disagree on whats appropriate and whats not appropriate.What complicates things here is that its not really an all or nothing decision. There are different scenarios where you could see parents using gene-editing on behalf of their unborn children.

I like to break it down is three scenarios. The first scenario is with parents who have medical issues that make it so that theres no way they can have natural biological children or healthy babies if they both have a bad disease and theyre going to pass it on to all of their kids unless you do something like editing. These are unusual situations, but they do exist.

The second scenario is one where parents might want to quite understandably reduce the risk of their child having some serious illness at some point in their lifetime. Im talking about things that are fairly common, like Alzheimers disease or breast cancer or heart disease or whatnot. Theres no guarantee that the editing will eliminate that risk. But you can see how parents might want to stack the odds in their kids favor. Its still medical, but its not perhaps as severe a situation with a kid whos definitely going to get the disease unless you do something.

The third scenario would be cases in which parents want to make changes that are not really medical but are more of what we would think of as enhancements. These could be cosmetic changes like hair color, eye color, things like that.

But it could potentially be much more serious things like intelligence or athletic ability or musical talent. Now, to be fair, thats theoretical. I dont think we are anywhere near knowing enough about how genes influence these things to be able to do it anytime soon. You might actually have to change hundreds of genes in order to make those changes. But you can imagine how certain parents might want to do that, might want to advance their children in the ways that they feel personally are desirable.

Bowman: Can gene editing only be performed on embryos or is it possible to edit genes in later stages of pregnancy or even post-birth?

Musunuru: Theres actually a lot of exciting work going on using gene editing to help patients, whether its adults or children. Right now its been focused mostly on adults who have terrible diseases and its really being used as a treatment to alleviate their suffering or potentially cure the diseases.

Just recently, we got the exciting news that two patients one in the U.S. and one in Europe were participating in a clinical trial. They each had a severe blood disorder. One of them had sickle cell disease. The other had a disease called beta-thalassemia. Earlier this year, they got a CRISPR-based treatment. And whats very exciting is that it looks like not only have their conditions improved significantly, it looks like they might actually be cured.

If that bears out, it would really be historic because these are diseases that affect millions of people around the world and were previously incurable. This treatment is also being explored for things ranging from cancer to liver disease to heart disease.

So theres enormous potential for benefit for living people who have serious diseases. But its a very different situation than editing embryos because youre talking about a person who is in front of you. We are trying to alleviate their suffering. That patient has the ability to freely give consent to the procedure, to weigh the benefits and risks and come up with a decision.

Bowman: How does that work? Is it some kind of cell transplant where the new cells then replicate throughout the rest of the body?

Musunuru: Yeah. It depends on the situation. I mentioned those two patients with the blood disorders. The way it worked there was the medical team used bone marrow stem cells. They basically took bone marrow as if they were going to do a transplant and then edited blood stem cells in a dish outside of the body to fix the genetic problem. And then they took those edited stem cells and put them back into the same patient. Those cells start making the blood cells that are now corrected or repaired. And by doing that, to cure the disease.

Another potential implementation is I work on heart disease. And what wed like to be able to do is turn off cholesterol genes in the liver. So what I envision is that a patient with heart disease would get a single treatment and it would deliver CRISPR into the liver and just the liver. It would turn off genes that produce cholesterol in the liver. The effect of that is permanent reduction of cholesterol levels and lifelong protection against heart disease.

This actually works really well in mice. Ive been working on this in my own laboratory for six, almost seven years now experimenting with it in monkeys. And if looks like it works and Im pretty confident that it will work we could be looking at clinical trials in a few years where were taking patients who have really bad heart disease or a very high risk for heart disease and actually giving them the single treatment within their own bodies that would turn off these cholesterol genes.

Bowman: In terms of more cosmetic applications, theres this popular idea that designer babies will be a reality at some point in the future. But how feasible would it be to use gene-editing for something very basic like choosing eye color or hair color? Are there many genes involved in determining traits like that? Are we close to being able to do that if we choose to?

Musunuru: Well, eye color, hair color, those actually turned out to be fairly simple. Theres only a small number of genes that control those. So in theory, if you wanted to do it, it wouldnt be that difficult.

Personally, my point of view is thats a trivial thing. Like why would you go through all that trouble? Do I care if your kid has blue eyes versus green eyes versus brown eyes? Maybe some parents feel that thats very important. So I think simple things like hair color, like eye color, it could be done fairly readily. I just dont see it as serious enough to warrant doing it.

The more complex things like intelligence, gosh, thats going to be so challenging. I mean, intelligence is just such a complex phenomenon. Theres some genetics involved in it, but there are so many other factors that come into that like upbringing and environment. Were not even getting close to an understanding of how someones intelligence comes about, to be perfectly honest about it.

I will point out that even though some of these things are simpler, in general, the vast majority of people are very, very uncomfortable with the idea of using gene editing of embryos for enhancements.

And I think this reflects a couple of things. I think this reflects the fact that people are more sympathetic if something like this is being used for medical purposes and much less comfortable if its being done to give a child an advantage in a way thats not medical.

It brings to mind the recent scandal where wealthy parents were trying to get their kids into good colleges by actively bribing admissions officers, faking test scores, fabricating resums. That kind of thing makes people very uncomfortable that certain people, particularly wealthy people, might try to use this technology to an extreme to advantage their children.

Theres an economic aspect to that. Wealthy parents might have better access to this technology than those who are not as wealthy. And what does that mean? If wealthy parents are somehow able to make designer babies who somehow are advantaged and other people are not, does that exacerbate socio-economic inequalities in our society?

So I think there are a few reasons why people are uncomfortable with the idea of enhancement, whereas on the whole, the majority seem to be at least somewhat open to the idea that there might be good medical uses.

Bowman: Im really happy that you brought up that socio-economic inequality aspect because I was going to ask you about that. But if we table those concerns for a moment and go way out there, theres this notion you write about that we could ultimately, theoretically, control our own evolution.

Ive heard it suggested that it could be theoretically possible to incorporate traits from other organisms that could be advantageous into our own DNA and essentially enter a new post-human stage of evolution. Is that total science fiction or do you think were entering a period where that is increasingly possible?

Musunuru:Well, with the way things are going with this technology. I mean, weve taken a step towards that. But there are many, many, many, many steps that would need to be taken to actually get to that point. But I think youre right. You see the path. We have the technology. Then its a question of perfecting the technology. A question of learning more about what genes from other species might be advantageous.

The cats out of the bag. The technology is here. Whether its five years from now or 10 years from now or 50 years from now or 100 years from now, these sorts of things will inevitably start to happen. And Im not sure theres much that those who would like to not see that happen will be able to do to stop it in the long run.

China Jails Scientist Who Gene-Edited Babies

Read the rest here:
Controlling Our Own Evolution: What is the Future of Gene-Editing? - The Globe Post

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized. Bone stem cells have been found both in the bone marrow and in the outer layer of tissue, called periosteum, that envelopes the bone. Of the two, periosteal stem cells are the least understood.

Having a better understanding of how adult bones heal could reveal new ways of repair fractures faster and help find novel treatments for osteoporosis. Dr. Dongsu Park and his colleagues at Baylor College of Medicine investigate adult bone healing and recently uncovered a new mechanism that has potential therapeutic applications.

Previous studies have shown that bone marrow and periosteal stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms, said Park, who is assistant professor of molecular and human genetics and of pathology and immunology at Baylor.

It is known that these two types of bone stem cells comprise a heterogeneous population that can contribute to bone thickness, shaping and fracture repair, but scientists had not been able to distinguish between different subtypes of bone stem cells and study how their different functions are regulated.

In the current study, Park and his colleagues developed a method to identify different subpopulations of periosteal stem cells, define their contribution to bone fracture repair in live mouse models and identify specific factors that regulate their migration and proliferation under physiological conditions.

The researchers discovered specific markers for periosteal stem cells in mice. The markers identified a distinct subset of stem cells that showed to be a part of life-long adult bone regeneration.

We also found that periosteal stem cells respond to mechanical injury by engaging in bone healing, Park said. They are important for healing bone fractures in the adult mice and, interestingly, they contribute more to bone regeneration than bone marrow stem cells do.

In addition, the researchers found that periosteal stem cells also respond to inflammatory molecules called chemokines, which are usually produced during bone injury. In particular, they responded to chemokine CCL5.

Periosteal stem cells have receptors molecules on their cell surface called CCR5 that bind to CCL5, which sends a signal to the cells to migrate toward the injured bone and repair it. Deleting the CCL5 or the CCR5 gene in mouse models resulted in marked defects or delayed healing. When the researchers supplied CCL5 to CCL5-deficient mice, bone healing was accelerated.

The findings suggested potential therapeutic applications. For instance, in individuals with diabetes or osteoporosis in which bone healing is slow and may lead to other complications resulting from limited mobility, accelerating bone healing may reduce hospital stay and improve prognosis.

Our findings contribute to a better understanding of how adult bones heal. We think this is one of the first studies to show that bone stem cells are heterogeneous, and that different subtypes have unique properties regulated by specific mechanisms, Park said. We have identified markers that enable us to tell bone stem cell subtypes apart and study what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries.

Find all the details of this study in the journal journal Cell Stem Cell.

Other contributors to this work include Laura C. Ortinau, Hamilton Wang, Kevin Lei, Lorenzo Deveza, Youngjae Jeong, Yannis Hara, Ingo Grafe, Scott Rosenfeld, Dongjun Lee, Brendan Lee and David T. Scadden. The authors are affiliated with one of the following institutions: Baylor College of Medicine, Texas Childrens Hospital, Pusan National University School of Medicine and Harvard University.

This study was supported by the Bone Disease Program of Texas Award and The CarolineWiess Law Fund Award, the NIAMS of the National Institutes of Health under award numbers 1K01AR061434 and 1R01AR072018 and U54 AR068069 and the NIDDK of the NIH.

By Ana Mara Rodrguez, Ph.D.

Here is the original post:
There is a new player in adult bone healing - Baylor College of Medicine News

DNA inherited from Neanderthals and Denisovans may have provided humans with protection against infectious diseases, including malaria, a study published in Neuron suggests.

Researchers also found added evidence that these inherited genes could affect biological processes and neurological conditions like autism and attention deficit/hyperactivity disorder (ADD).

For over a decade, scientists have suggested modern humans interbred with other hominin species, including Neanderthals. Evidence of this interbreeding can still be found in the DNA of people living today.

Genomic introgression is where DNA is swapped when two species interbreed. This can result in traits and characteristics being passed from one species to the other.

An example of this is Tibetans' unique aptitude for high altitude living, which is thought to have stemmed from their early ancestors interbreeding with Denisovansanother extinct archaic species from the Homo genus.

Less advantageous traits that we may have inherited from our non-Homo sapien ancestors include depression and social anxiety, as well as an increased susceptibility to inflammatory diseases like type 2 diabetes.

It is thought that Neanderthal ancestry for non-African populations sits somewhere between the 1 and 4 percent mark, though ranges vary. Melanasians and East Asian populations are also thought to carry Denisovan DNA, with up to 5 percent of Melanesian DNA derived from Denisovans by some estimates.

Typically, scientists have attempted to understand these genomic introgressions by studying the genes themselves, the researchers say. In this research, they focused on the relationships and interactions between genes, which were sourced from the 1000 Genomes Projecta catalogue of human genomesand 35 Melanesian individuals.

"Our results suggest that gene interactions and associations between different archaic mutations have played an important role in human evolution," Alexandre Gouy, one of the study authors, from the University of Bern, Switzerland, told Newsweek.

Some of the inherited genes analyzed in the study have been linked to autism and ADD. Others are thought to influence biological processes, such as energy metabolism. But some of the most intriguing mutations looked at were those related to protections against infectious diseasesand malaria in particular, said Gouy.

"When looking at immunity genes ... it was interesting to see that they were involved in the response to all kinds of pathogens: virus, bacteria and protozoanssuch as the malaria parasite," he said.

This suggests DNA inherited from extinct hominids bolstered the human immunity to infectious diseases, adding to existing research that suggests interbreeding with Neanderthals improved humans resistance to infections and susceptibility to allergies.

One of the "most striking" findings was evidence of an adaption in the genes of Papua New Guineans inherited from ancient hominids, which may provide some kind of protection against malaria.

However, the researchers are keen to stress their findings are preliminary. While it is becoming increasingly evident that humans have adopted genes from ancient hominids, it is unclear how this affects people in the 21st century.

"It remains very difficult to quantify precisely the effect of those mutations," Gouy said. "Health and behaviour result from the interaction of a complex genetic background and the environment. Hence, the impact of genetics on the immune system and behaviour is difficult to assess."

Read the rest here:
Ancient Hominids May Have Helped Protect Humans From Malaria - Newsweek

Charles Boone first set foot in Japan fresh out of undergrad in 1983 when he lived and worked with a local family on a rice farm in Chiba prefecture, just outside Tokyo. There, he fell in love with many things Japanese not least its cuisine, which owes much of its flavourto fermenting microorganisms.

Now, years later, the microbes would lure Boone back to Japan, albeit for a different reason.

So many of the drugs we use today have come from microorganisms, says Boone. And theres still an enormous untapped potential out there.

Over the last decade, Boone has been working with Minoru Yoshida and Hiroyuki Osada, both professors at the RIKEN Centre for Sustainable Resource Science, to identify new compounds from microbes with the potential to be research tools and pharmaceuticals.

Another Donnelly investigator and U of T professor, Andrew Fraser, is also collaborating with the RIKEN teams to find new drugs that target parasites.

Surrounded by cherry trees on a research campus just outside Tokyo, the RIKEN Centre houses the worlds largest collection of natural compounds some 40,000 chemicals and other derivatives produced mainly by soil microbes and plants, as well as some synthetic compounds.

The RIKEN collection is exceptional because it contains so many pure natural products says Boone. This makes it easier to investigate how those molecules might be acting on living cells.

Collected by Osadas team over the last 15 years, the medical potential of the vast majority of compounds remains unexplored.

We still dont know why the microbes are producing these compounds, says Yoshida.

It could be that microbes are using these chemicals as weapons against other microbes or as communications tools, as most of them seem to be non-toxic. Whatever the reason behind their making, the researchers hope to tap into this chemistry for new molecular tools and drugs.

Its no coincidencethat Japan has such a rich resource of natural compounds. The country has a long tradition of microbial exploits in the production of food and drink. Take the rice wine sake, for example. It involves the sophisticated use of a filamentous fungus to transform pure rice into a suitable carbon source for fermentation by yeast cells.

The microbial know-how allowed Japanese scientists to discover, in the second half of the 20th century, more than 100 new antibiotics, as well as the anti-parasite blockbuster drug ivermectin, a finding that was recognized by a Nobel Prize in 2015.

Drug applications came naturally out of using microbes for food fermentation, says Yoshida, whose 1990 discovery of trichostatin A, a drug that interferes with how the DNA is packaged inside the cells, from a Streptomyces bacteriumtransformed the study of epigenetics and led to similar compounds that are being trialed on patients as a treatment for cancer and inflammation.

According to a recent study, the majority of approved medications come from nature, or are synthetic molecules inspired by the natural products. Infection-fighting antibiotics and cyclosporine, an immunosuppressant that has made transplant medicine possible, are prominentexamples.

Natural products make good drugs because they were honed by evolution to act on living cells, says Yoshida. They tend to be large and structurally diverse molecules that engage with their cellular receptors more specifically than the purely synthetic drugs, meaning they can be used at low doses and elicit fewer unwanted side effects.

Despite their clear potential, the pharmaceutical industry has shifted its focus from the natural compounds, which are also difficult to purify and synthesize on an industrial scale, to searching for drug candidates among large pools of synthetic chemicals.

But Boone thinks this may be a mistake.

It seems ridiculous to be shunning natural products given that the majority of drugs we use today have come from nature, says Boone. And our work suggests that there are a lot of compounds out there that could be useful for research and also medicine.

A 2017 study by Boone, Yoshida and Osadas teams found that the RIKEN collection holds more medically promising compounds than several stockpiles of synthetic chemicals widely used in research. They did this by identifying the molecular mechanism of action for thousands of compounds, using a large-scale application of the yeast cell-based chemical genomics platform, developed by Boones lab in the Donnelly Centre. Many of these housekeeping processes in yeast cells are also found in human cells and have been implicated in a variety of diseases, from cancer to Alzheimers.

But, there are many more compounds left to test.

More recently, Sheena Li, a post-doctoral researcher who worked in Boones lab at RIKEN, where he holds a joint appointment, and has since moved to the Donnelly Centre, found that one compound from the RIKEN collection acts as a powerful antifungal by blocking an important enzyme in yeast cells. As such, the compound holds promise for the treatment of drug-resistant fungal infections, which are becoming a serious global health threat.

Taking all their data into account, Li says they have identified about 50 products with medical potential. The next step is to check if these chemicals act in the same way in human cells.

Its a great step forward to be able to take something that you invested so much time studying in yeast into the human system, Li says.

Unlike Boone and Li, Fraser is not interested in compounds that work in human cells quite the opposite.

We want to find new drugs against intestinal parasites, he says . But we do not want to harm the humans infected with these parasites.

Gut worm parasites affect around one billion people globally, 880 million of them children, according to the World Health Organization. As the parasites are becoming resistant to frontline treatments, including ivermectin, new drugs are urgently needed.

Since ivermectin was discovered in a soil microbe, Fraser thinks theres a good chance more future treatments are to be found at RIKEN.

His team recently developed a method to screen for drugs that target an unusual type of metabolism that only exists in parasites. This type of metabolism does not require oxygen for energy production and allows parasites to survive inside the hosts body for long periods of time.

Because parasites are difficult to cultivate in the lab, Frasers team found a way to trick the harmless worm and staple research tool, C. elegans, into using the oxygen-independent metabolism and look for drugs that affect it.

Any drug candidates will only target the worms without causing harm to humans, who do not have the ability to make energy the same way as the parasites.

The next step for Fraser is to see if there any compounds in RIKENs trove that act on those targets.

The RIKEN natural product collection is like an incredible collection of intricate tools the challenge is to figure out which targets each compound affects, and how we can use them to kill pathogens and enhance our health, he says.

Here is the original post:
Drugs from nature: Researchers from U of T, Japan mine microbial compound library for new therapeutics - News@UofT