June 20, 2017 by Silke Schmidt Megan McClean and Cameron Stewart have built a novel optogenetic system that monitors light-controlled yeast gene expression. This optostat regulates cellular processes, similar to how a thermostat controls room temperature. Credit: Stephanie Precourt

A user-friendly switch for controlling room temperature, the thermostat is a classic example of the kind of tools engineers build.

For biological systems research, Megan McClean and Cameron Stewart have taken the idea of a thermostat several steps furtherand using their invention, which combines the power of light, computers and genetics, researchers can now build an "optostat" that is remarkably similar to the thermostat in our homes.

"All you need is three ingredients," says McClean, an assistant professor of biomedical engineering at the University of Wisconsin-Madison. "An organism that grows well in cell culture, the ability to insert a light-sensitive switch into its genome, and a computer-controlled microscope that images what you want the organism to produce."

The optostat is a fully automated system that connects these three ingredients with electronics and freely available software. Using the light-responsive part of a plant protein to control the expression of a single gene in baker's yeast, the researchers were able to record images of the fluorescent protein produced by that gene continuously for up to 10 days, capturing how the cells responded to the amount of light they received. While light controlled the expression of the gene of interest, it did not affect the transcription of thousands of other yeast genes.

The system contains everything the cells need to grow in excess, except for one limiting nutrient that is provided through controlled release. Like a thermostat, the optostat can automatically adjust the amount of light needed to obtain a desired protein concentration.

Stewart and McClean recently described their optogenetic system in the Journal of Visualized Experiments, allowing other researchersespecially biologists without an engineering backgroundto set it up in their own labs.

Stewart compares their invention to a car's cruise control system. "Cars, throttles, and speedometers already existed, but cruise control combined them with a feedback system," he explains. "In our case, growing cells in a 'chemostat' to maintain a constant growth rate has been possible since the 1950s. But our novel contribution is to connect this chemostat to a light bulb to administer inputs, and to a microscope to measure outputs."

The new optostat is the only system of its kind that can sample and monitor the same cell culture continuously over a long period of time. This allows researchers to study any biological pathway of interest by tuning a single parameter and keeping everything else, including the cells' growth rate, the same.

Optogeneticsthe use of light-sensitive proteins as regulators of a variety of cellular processeshas been a growing research field for the last ten years, McClean says. Since the response of plants to light has been studied extensively, plant-derived proteins make ideal optogenetic tools.

One application of optogenetic systems that McClean is particularly interested in involves Candida albicans, the most common of more than 20 species of yeast-like fungi that live in our intestinal tract. They are usually harmless, but their overgrowth can trigger infections in certain body parts, such as the mouth or throat (thrust) and the vagina (yeast infection). When the fungus enters the bloodstream and spreads through the body, it may cause dangerous invasive infections.

Some Candida species have recently caused severe illness in hospitalized patients and are now considered a global health threat. "Our drug arsenal for fungi is very limited because these organisms are so similar to our own cells," McClean says. "That makes their emerging resistance to antifungal drugs especially disconcerting."

Candida species are a threat to hospitalized patients because they tend to form a thin mat, or biofilm, on hip or knee implants and intravenous catheters. By controlling different regulators of C. albicans growth with a light-sensitive switch, McClean hopes to learn what makes the organism change from its stable form in a biofilmlong and skinnyto its less stable, round form that may pop off the biofilm and disperse into the bloodstream. In the future, that knowledge may help inhibit fungal infections in humans without causing toxic side effects.

"One of the unique aspects of fungal biology is its potential to disperse into the bloodstream," McClean says. "In order to study the factors that cause it, we need a controllable system that allows time for a biofilm to form and then make light-induced perturbations. With several modifications we plan to implement next, we believe our optogenetic system will eventually provide that kind of tool."

Explore further: All yeasts are not created equal

Yeast. Great if you want to make bread or wine. Not so hot if it turns up as Candida albicans in large quantities in your body and makes you sick.

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A user-friendly switch for controlling room temperature, the thermostat is a classic example of the kind of tools engineers build.

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Building a biological control switch with light, genetics, and engineering ingenuity - Phys.Org

Ron (Rupert Grint), Hermione (Emma Watson), Harry (Daniel Radcliffe) and Ginny (Bonnie Wright) gather at platform 9 and 3/4 to send the next generation of witches and wizards to Hogwarts, in "The Deathly Hallows: Part 2" (Warner Bros. Pictures, 2011).

WASHINGTON In the world of "Harry Potter," magical ability runs in the family. Witches and wizards have parents who are witches or wizards, and they are typically born into families that have already produced generations of wand-wielders.

There are exceptions to this rule Hermione Granger was born to a pair of Muggles (people without magical powers), and Harry's roommate, Seamus Finnigan, was the son of a Muggle father and an Irish witch.

And sometimes, a witch and wizard couple will produce a non-magical person known as a squib such as the cranky Hogwarts caretaker Argus Filch, or Harry's Privet Drive neighbor and childhood babysitter, Arabella Figg. Magic appears to follow some of the same rules as other traits that are inherited, but what could be the genetic factors that explain why someone is born a witch or a wizard or without any magical ability at all? [Science Fact or Fiction: The Plausibility of 10 Sci-Fi Concepts]

A roomful of people here at Future Con got a crash course in wizarding DNA and the basic workings of genetics on June 17, at a talk hosted by Eric Spana, an assistant professor in the Department of Biology at Duke University, in North Carolina.

Genetics can explain more in the "Potterverse" than just magical ability like the Weasley family's signature hair color, for example. Red hair is caused by a mutation in the MC1R gene; but it's a recessive trait, which means it crops up only when the mutation is present in both sets of DNA that a child inherits. Arthur and Molly Weasley are both redheads, thereby ensuring that their offspring would inherit two copies of the gene mutation, and would be born with red hair, Spana explained.

However, in the very last scene of the final movie, "The Deathly Hallows: Part 2" (Warner Bros. 2011), we see that Harry and Ginny's young daughter Lily has red hair, even though Harry's hair is brown. In that case, the gene mutation came from Harry's copy of his mother's DNA. His mother had red hair, so he inherited the mutation but it couldn't do anything until it encountered a second copy of the mutated gene in Ginny Weasley's DNA, Spana said.

Eric Spana, an assistant professor in the Department of Biology at Duke University, describes wizard DNA at the Future Con panel, "Harry Potter and the Genetics of Wizarding."

Is the wizarding gene recessive, like the gene for red hair? Hagrid, the half-giant-half-wizard groundskeeper at Hogwarts, proves that it isn't, according to Spana. Giants have no magical ability, and Hagrid was born to a giant mother and a wizard father. For him to be born a wizard with only one copy of the wizard gene in his DNA, magical ability would have to be a dominant trait, Spana said.

This example seems to hint that magic is linked to the Y chromosome, which means the gene would have to come from the father's DNA (females have two X chromosomes, while males have one X and one Y chromosome). However, Seamus Finnigan had a Muggle father and a witch mother, which suggests it can't be the Y chromosome that carries the gene. That would make wizarding ability something called an autosome a trait that isn't linked to sex characteristics, Spana said. [Unraveling the Human Genome: 6 Molecular Milestones]

"It's an autosomal, dominant trait," he concluded.

But if it's a dominant trait, then where did Hermione's magic come from, as the first witch to be born in her family? Hermione is an example of a "de novo" mutation a genetic mutation that appears in a lineage for the first time, due to a mutation in the egg or sperm, or within the embryo itself following fertilization. And this type of mutation occurs quite frequently in real life, Spana said.

A random mutation could also explain how a non-magical squib could be born to two magical parents, he added.

If the wizarding gene is working correctly, it makes a certain type of protein. The phenotype, or observable characteristics resulting from that activity, is magical ability. But if there's a mutation in that gene Spana suggested calling it the "SQUIB" mutation a different type of protein turns the magic gene off. If one parent's DNA carries a copy of the SQUIB mutation, it can turn off the wizarding protein, which cancels a child's ability to do magic.

"We do this in fruit flies all the time," Spana said, referring to manipulation of hereditable traits in general and not of genes for magic.

And then there are individual variations in wizarding ability, with some witches and wizards recognized to be more powerful than their fellows. Could genetics explain that as well? Not entirely, Spana said.

"I come from the 'basketball school' genetics makes you 6-foot-8, but it doesn't give you skill. Working at it gives you skill," Spana said. Hermione's power, as well as the varying degrees of expertise demonstrated by the Weasley children, suggests that one's magical ability is not completely reliant on genetics, he said.

As the discussion drew to a close, an audience member asked Spana the one question that must accompany any serious conversation about the Potterverse: Which Hogwarts house would the Sorting Hat have placed him into?

"I'm 100 percent Slytherin or as I like to call it, 'Management,'" Spana said.

Original article on Live Science.

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Genetics of Wizardry: Were Harry Potter's Magical Powers Written in His DNA? - Live Science

Seattle Genetics Inc. SGEN, +0.61% said Monday that it is discontinuing the Phase 3 clinical trial of its acute myeloid leukemia treatment, SGN-CD33A, after data indicated a higher rate of deaths, including fatal infections. The company said it will suspend patient enrollment and treatment, and will closely review the data and consult with the Food and Drug Administration to determine future plans. "This is a disappointing and unexpected result for the CASCADE trial. Patient safety is our highest priority, and we will closely review the data and evaluate next steps," said Chief Executive Clay Siegall. The stock, which is still inactive in premarket trade, has rallied 22% year to date through Friday, while the iShares Nasdaq Biotechnology ETF IBB, +2.10% has climbed 10% and the S&P 500 SPX, -0.52% has gained 8.7%.

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Seattle Genetics suspends trial of leukemia treatment after data showed higher rate of death - MarketWatch

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.

Read more:
Genetics Might Be Settling The Aryan Migration Debate, But Not How Left-Liberals Believe - Swarajya