Clay Siegall, CEO, Seattle Genetics

In the wake of Seattle Genetics announcement that a disturbing tilt in deaths pointed to a likely safety problem for its late-stage cancer drug vadastuximab talirine (SGN-CD33A), the FDA has stepped in to yank the IND and officially put any human testing on hold.

The biotech $SGEN reported the FDAs move in a filing with the SEC this morning.

Seattle Genetics had already hit the brakes on its R&D work on the drug three days ago, scrapping the Phase III for acute myeloid leukemia and ordering a halt to any other testing until they can get a better read on the situation. It will also have to convince regulators that the drug is safe for testing after the FDA had lifted its first clinical hold on the drug just three months ago. That first hold on its early-stage work came after four patients died.

Those deaths were linked to liver toxicity, a classic red flag on safety. But this time one of the few clues provided by Seattle Genetics is that liver toxicity did not appear to be behind the disturbing rate of deaths investigators were seeing.

Back in March the biotech reported that it was getting restarted on the clinical work after it came up with revised eligibility criteria and stopping rules for veno-occlusive disease.The FDA agreed to lift the hold only two months after it was dropped on Seattle Genetics.

With its big Immunomedics deal axed by activists and its lead clinical drug in big trouble, Seattle Genetics CEO Clay Siegall will come under heavier pressure to diversify beyond Adcetris.

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FDA padlocks any new human tests on Seattle Genetics' cancer drug in the wake of more deaths - Endpoints News

TALLAHASSEE, Fla. (CAPITOL NEWS SERVICE) A member of the Florida State University Board of Governors is in hot water, after making a comment at board meeting in which he seemed to suggest differences in starting salaries between men and women maybe genetic and not cultural.

The comment spurred a backlash.

Floridas Board of Governors was told that statistics show women graduates make less than their male counterparts a year after leaving school.

Board member Ed Morton suggested teaching salary negotiating skills for women, but also said the gap may be genetic. The women are given, maybe some of its genetic, I dont know. Im not smart enough to know the difference, he said.

Morton, who was appointed by Governor Rick Scott, was quickly condemned by the Governor in a statement issued by his press secretary.

As a father of two daughters, the Governor absolutely does not agree with this statement.

Morton has since apologized, issuing a statement, but refusing interviews. He says in part I chose my words poorly. My belief is that women and men should be valued equally in the workplace.

The controversy comes after legislation failed in the 2017 regular session that attempted to close the wage gap between men and women.

More women than men graduate from Florida universities, still womens median starting salaries are $5,500 less than men, said Jake Stofen.

Dr. Wayne Hochwarter a professorof Organizational Behavior at FSU says the gap is more likely a result of women choosing professions that pay less.

Whereas you still have a large section of young men who are also in the business school and engineering, he said.

Hockwarter also says research shows women often times are better prepared and better equipped for situations like negotiating salaries.

STORIES OTHERS ARE CLICKING ON:

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FSU boardmember suggests women's salaries may be lower due to genetics - WFLA

Anyone who has sat through a high school biology lecture on genetics understands the basics of dominant and recessive alleles, which explain, among other things, how two brown-eyed parents can have a blue-eyed baby.

When you start talking magical ability, however, things become more complicated.

That was the topic of one panel at Future Con, a conventionwhere science meets science fiction, held this past weekend. In Harry Potter and the Genetics of Wizarding, Duke University professor Eric Spana discussed the intricacies of wizard DNA.

Fans of Harry Potter know that, while two magical parents will likely have magical children, thats not always the case. Occasionally, an all-magic union will result in a squib, or non-magic, child (think of poor Argus Filch, tasked with cleaning all of Hogwarts without so much as a wand to help him out). On the flip side, Hermione Granger one of the finest witches of all time, IMO was born to two muggle parents. Throughout the series, we learn that students like Seamus Finnigan had one magical and one muggle parent. So how the heck is magical ability passed on?

According to a summary of the panel from Live Science, Spana debated whether magical ability was a recessive trait (much like the Weasley familys red hair), meaning its possible for an individual to carry the gene and potentially pass that gene onto offspring without expressing its traits. He ultimately decided it wasnt, though thanks to one Rubeus Hagrid.

You see, Hagrid was born to a giant mother and a wizard father. This meant Hagrid was born a wizard with only one copy of wizarding DNA in his blood (giants are non-magical). Thus, Spana concluded, magical ability must be a dominant trait.

If thats the case, how did Spana explain children like Hermione, who are the first in her family line with magical powers? A good, old-fashioned genetic mutation, possibly occurring in a sperm or egg cell, or after the egg is fertilized. (Yeah, dont you wish youd remembered more from AP Biology now?) As for squibs, Spana posited that parents could carry a mutation of the wizarding gene and pass it on to their child.

Science, man. Its pretty magical.

From June 1 to 30, HuffPost is celebrating the 20th anniversary of the very first Harry Potter book by reminiscing about all things Hogwarts. Accio childhood memories.

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Here's How A Duke Professor Broke Down Wizard Genetics In 'Harry ... - HuffPost

I generally avoid the biotech/health tech space, but the Myriad Genetics (NASDAQ:MYGN) story is simple enough to understand and evaluate. After riding high for years, the company came under pressure within its core competency: hereditary cancer diagnostics. Diversification and M&A efforts have proven to not be enough to stem the tide of margin erosion from fresh competition, and within a beaten-down sector that values growth highly, it shouldn't be a surprise that the shares have seen their value cut in half over the past two years. 2017 has been a year of recovery for shares, particularly over the last two months. As a fan of the company's business model and story, I'm glad to see it finally building a base. As an investor, however, the question remains simple: Does Myriad Genetics have long-term value potential, and is now the time to buy?

Business Overview, Long-Term Outlook

Founded in 1991 and based out of Salt Lake City, Myriad Genetics focuses on the development and marketing of predictive prognostic medicine tests. Diagnostics the company provides allow the assessment of an individual's risk for developing a disease, identifying the likelihood a patient will respond to certain drug therapies, the risk of recurrence/rate of progression, or providing guidelines for dosing. As a staunch critic of how the United States healthcare system is run, any company that helps to drive down overall costs via the elimination of misdiagnosis and improving early detection, all while improving patient welfare, is going to tend to be in my good graces.

Tests include, but are not limited to, BRACAnalysis and BART (hereditary breast and ovarian cancers), COLARIS (colorectal/uterine cancers), and myPath Melanoma (RNA expression test for melanoma). Overall, Myriad targets six medical specialties: oncology, dermatology, autoimmune, urology, neuroscience, and preventive care. According to the company (as sourced from Clinical Lab Products magazine), diagnostic tests represent just 3% of overall healthcare spending domestically but drive 70% of healthcare decision-making. Figures vary depending on where you look, but overall consensus is that there's hundreds of billions of dollars in wasteful spending in the United States health market, and proper testing and diagnostics could help eliminate a meaningful percentage of that waste.

Strategically, the company wants to hit double-digit revenue growth and improve the international revenue base, all while maintaining a better than 30% operating margin. That's a tall order, particularly given that hereditary cancer revenue, the company's core competency, has been tailing off since fiscal year 2014. While Myriad Genetics does likely have some differentiation due to first-mover advantage (twenty years of experience, nearly 3M patients tested, has identified tens of thousands of variants), the problem keeps coming down to average selling prices ("ASPs"). In the most recent quarter, for instance (Q3 of fiscal 2017), Myriad Genetics grew hereditary cancer testing volumes in a tough quarter seasonally for the first time in five years. Great, right? The problem was hereditary cancer revenue fell 10% y/y, an acceleration from the drop from the 2015/2016 comp drop. The entire decline is therefore attributable to pricing; management also points to revenue recognition delays from an Anthem (NYSE:ANTM) out-of-network decision as well, which is set to continue into the next quarter.

As goes hereditary cancer products, so does consolidated revenue. Revenue was up 3% in fiscal Q3 2017, but only due to the acquisition of GeneSight products ($24 million in revenue contribution), which were added based on the August 2016 acquisition of Assurex Health ($225 million in cash, potential for $185 million in additional payments based on performance milestones). Growth has been great there, with revenues up 44% y/y (7% sequentially). A product from another key acquisition, Vectra DA (acquired from Crescendo Bioscience for $245 million in cash), unfortunately posted y/y declines (9%). However, this quarter marked a return to sequential growth after the company clarified some issues relating to a study with negative results. That ties into the ongoing situation with Medicare non-coverage, but Myriad Genetics is optimistic that there will be a favorable resolution. Supporting data is on the way, with the company recently announcing the completion of enrollment in a 1,200-person clinical study which will provide data within calendar year 2017. Prolaris posted revenue declines, mostly due to a Medicare retrospective payments unfavorable comp last year. Volumes were up, breaching the 20,000 annual run rate for the first time. The comment period on the Medicare Favorable Intermediate LCD concluded recently, and if Medicare confirms, it will expand reimbursement coverage by 50%.

While there are negatives here (namely, volume growth at the expense of ASPs), Myriad spins these business lines as having serious potential, primarily due to higher ASP outlook. The majority of these products have issues with insurance non-coverage, which drives down ASPs to cash-paying customers that want access, as well as denting volume. Driving greater commercial insurance adoption is a key goal, and one that is central to the underlying investment thesis. If Myriad Genetics cannot prove out that its products can save insurance companies significantly - by the company's estimates hundreds of millions per year for large payers - then it is going to struggle.

There are nearly a dozen clinical studies that will conclude over the next two years that could boost visibility of the company's products, particularly in metastatic breast, ovarian, and pancreatic cancers, which could lead to adoption. With that said, I am not convinced that ASPs will see the rise management is expecting. A lot of existing large payer contracts within hereditary have seen pricing concessions in order to lock in longer deals, and I suspect there might be more pressure on pricing than expected. However, non-hereditary products do make up 68% of volume but only 28% of revenue. There is plenty of opportunity for expansion there, at least compared to hereditary as a baseline.

This is a likely reason why there is a strong focus on international sales. The European Union and Canada tend to be much quicker at adopting new technologies in the medical space, although pricing is often much lower than the United States. Expect Prolaris, Vectra DA, EndoPredict, and the various myPlan hereditary platforms to be pushed overseas. The international mix has picked up quite a bit since fiscal 2014 (<1% revenue) to 5% today, and I think it is a more than reasonable expectation that Myriad Genetics reaches its goal of 10% of revenue being sourced internationally by the end of fiscal 2020.

Roadmap To 2020, Valuation

For shareholders, growth of non-hereditary, both in volume and price, is paramount to a long thesis. Myriad Genetics has a goal of $1,200 million in revenue by fiscal 2020, but it also sees $300 million in run-off of revenue from hereditary, or basically a 50% haircut from current levels. To fill the gap, management is looking for 15% annual growth from the company's so-called stage three products (GeneSight, Vectra DA, Prolaris, EndoPredict), with considerably less emphasis on products not as far along in development. But importantly, the company bases this on 75% reimbursement, which requires significant increases in average selling prices:

*Myriad Genetics, 2017 Investor Presentation

Investors clearly believe in a turnaround; Myriad Genetics is now more expensive on trailing measures (EV/EBITDA, P/E) than it has been for most of its recent history. However, there is a lot of upside if the company can execute; fiscal 2020 would see EBITDA in the $430 million range based on management targets, enough to warrant the shares more than doubling in value (EV to $3,870 million on a 9x multiple, 132%). This is a story of execution and a little bit of faith in whether CEO Mark Capone and team are both setting realistic goals and have the clout to achieve them. Unfortunately, my expertise ends there, and I have no way of assigning a fair probability to achieving those goals. I've got to take a pass on the company as a result, but I can see why many investors are interested, particularly after the recent fall.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Myriad Genetics: Worth A Bet On Diagnostics Kit Pricing Expansion? - Seeking Alpha

A Florida college official said Tuesday that women make less money than men because genetically they might lack the skills to negotiate for better pay.

Edward Morton ofthe State University System of Florida made the comments during a board meeting in which members talked about closing the wage gap between male and femalegraduates of the states public university system.Morton, chair of the boards Strategic Planning Committee and a financial adviser from Naples, Fla., said,according to Politico:

Something that were doing in Naples some of our high school students, were actually talking about incorporating negotiating and negotiating skill into curriculum so that the women are given maybe some of it is genetic, I dont know, Im not smart enough to know the difference but I do know that negotiating skills can be something that can be honed, and they can improve. Perhaps we can address than in all of our various curriculums through the introduction of negotiating skill, and maybe that would have a bearing on these things.

Morton apologized for his comment in an email sent to fellow board members shortly after the meeting.

I chose my words poorly. My belief is that women and men should be valued equally in the workplace, he said, adding that the universitys goal is to teach all students how to better negotiate their salaries.

[Utah Republican argues against equal pay for women: Its bad for families and society]

Gov. Rick Scott, who appointed Morton to the board, was among those who quickly criticized Morton for hiscomments. Lauren Schenone, a spokeswoman for Scott, said in a statement that as a father of two daughters, the governorabsolutely does not agree with Mortonscomments.

Gwen Graham, whos seeking the Democratic nomination for governor,tweeted Tuesday night:When I sat at the negotiation table, nothing about my gender or genetics held me back. THIS is why we need more women in state government.

Morton did not return a call seeking comment Wednesday.

Politico reported that during the meeting board members were reviewing areport on gender wage gaps among students who graduated from the university system in 2015.The report, which looked at what students did after graduation and how much theyre earning, found that female graduates from various fieldshave an annual median salary of $37,000, which is $5,500 less than the median salary of male graduates. African American graduates make even less, with an annual median wage of $35,600.

[Here are the facts behind that 79 cent pay gap factoid]

Femalegraduates make less than men even though they account fornearly 60 percent of the graduating class, according to the report.Blacks, Hispanics and whites make up 12 percent, 25 percent and 52 percent of the graduating class, respectively.

During the meeting, Morton said that the wage gap will in some way be self-correcting because the university system has more female graduates than men, according to Politico.

The report also found significant discrepancies in pay among men and women who graduated with the same degrees.The median salaries of women with degrees in biological sciences, business and marketing, communication and journalism, security and protective services, social sciences, and visual and performing arts are from$1,200to $4,400 lower than those of men with similar credentials.The gap among agriculture, liberal arts and physical sciences graduates is even greater from $6,400to $9,400.

Yet the report also found that women with degrees in education, engineering, health professions and psychology make from$500 to$3,100 more than their male counterparts annually.

A history of the long fight for gender wage equality. (Daron Taylor/The Washington Post)

Florida is among more than a dozen states with equal pay laws that haveloopholes that allow employers to continue to pay women less, according to the American Association of University Women.Two states, Alabama and Mississippi, have no equal paylaws. And only a handful California, Illinois, Minnesota, Vermont, Massachusetts and Maryland have strong equal pay laws.

Nationally, womens annual earnings are about 80 percent of what men make, according to a recent report by the association.

The report attributes the wage gap partly to differences in career choices and to the fact that parenting more often puts womens professional lives at a disadvantage than it does mens. Twenty-three percent of mothers left the workforce 10 years after graduation, while 17 percent worked part-time, according to the association. Those numbers among fathers were 1 percent and 2 percent, respectively.

Despite factors such as life choices and parenting, women facepay gaps at every education level and in nearly every line of work, the report said.

READ MORE:

In the federal government, how likely is it that a woman will make more than a man?

The poor just dont want health care: Republican congressman faces backlash over comments

Nobody dies because they dont have access to health care, GOP lawmaker says. He got booed.

Continued here:
A Florida higher-ed official said women's genetics may be keeping them from equal pay - Washington Post

Accelerated Genetics in Westby may expand its operation following a potential merger.

Angie Lindloff, vice president of marketing and communications, said staff downsizing isnt likely to occur even if Accelerated Genetics is sold to the larger, Ohio-based Select Sires. It was recently announced the two companies, which specialize in artificial insemination of cattle, may combine forces.

Lindloff said that while there are no guarantees of job security, Westby employees could see more bulls in housing than before. She said Select Sires aims to increase local production for international markets.

My understanding is (Select Sires) wants to keep the Westby facility intact and the people intact, Lindloff said. The goal is, they want that facility to maximize production out of it. Its actually a good thing from a Westby standpoint.

Roughly 70 people work for Accelerated Genetics in Westby, Lindloff said. The municipality is home to multiple Accelerated Genetics production barns, an office and a distribution center.

Select Sires, theyre very interested in the assets at Westby and the people there, Lindloff said. They know what we do there and they understand we have a lot of valuable people.

The Accelerated Genetics production facility houses more than 200 bulls, staff veterinarian Katie Speller said. Speller said the bulls supply genes for Accelerated Genetics national and international markets, including in Europe, Asia, Africa and the Middle East.

Following a potential merger with Select Sires, Lindloff said the company could move to increase Westbys international production capabilities and bring in more cattle.

She said that barns producing semen for the European Union require special permitting, and Select Sires would aim to uptick the number of EU-certified barns in Westby.

Select Sires and Accelerated Genetics have an established business relationship. In 2001, the two companies began collaborative marketing efforts in foreign markets.

Select Sires is now poised to take over Accelerated Genetics, which has struggled financially.

We have been looking at something like this, something different than our current model, because we knew it was getting harder to do business, Lindloff said of Accelerated Genetics. So if we combine forces with somebody, it gives us more resources and just more opportunities to grow together.

Accelerated Genetics operates as a cooperative with member farms in Minnesota, Iowa, Wisconsin and Illinois. Under the potential acquisition, Accelerated Genetics member farms in those states would be rolled into one of Select Sires existing cooperatives.

Select Sires operates across the U.S.

Delegates from Accelerated Genetics are scheduled to cast final votes on the merger later this month. Select Sires did not return a phone call seeking comment by press time.

Read the rest here:
Accelerated Genetics may expand operations under new ownership - La Crosse Tribune

Every few years, J. Craig Venter of Synthetic Genomics and Exxon issue a joint proclamation about progress in biofuels derived from algae. Venter gets funded, Exxon gets green cred, breathless articles get written in the business press, and we are once again reminded that algae is the fuel of the future.

Venter has made brilliant contributions to modern genetics. He was part of the team that sequenced the second human genome.

Still, the team of Exxon and Synthetic Genomics have been working on algal biofuels since 2009, and although they are claiming a biofuel "breakthrough" in their latest release, the time frame for commercialization verges on generational as opposed to the decade-scale promises that have been made. Exxon called this a $600 million investment in 2009.

According to the most recent release, the partners have developed an algal strain that has "more than doubled its oil content without significantly inhibiting the strains growth." The research team claims to have modified the algae speciesNannochloropsis gaditana to stretch the algaes oil content from 20 percent to more than 40 percent. (That 40 percent figure has been tossed around by other researchers in recent years, as well.)

The release is careful to stress that this is deep research and "a proof-of-concept approach." Despite the laudatory articles being written, we are not much closer to commercial biofuels derived from algae oil.

In 2009, current U.S. Secretary of State and former Exxon CEO Rex Tillerson said that the venture might not produce real results for another 25 years.

Were still at the research phase in this program, cautions Vijay Swarup, a vice president at ExxonMobil, as quoted in Forbes. Its not just doubling [lipid production], but its understanding why it doubled and how it doubled," he said. "Theres still a long way to go in making an algae that can produce even more fat, live comfortably in saltwater pools outside, and be processed into fuel for cars, planes and trains."

The release notes that an objective of the collaboration "has been to increase the lipid content of algae while decreasing the starch and protein components without inhibiting the algaes growth. Limiting availability of nutrients such as nitrogen is one way to increase oil production in algae, but it can also dramatically inhibit or even stop photosynthesis, stunting algae growth and ultimately the volume of oil produced."

Bloomberg notes that the team "searched for the needed genetic regulators after observing what happened when cells were starved of nitrogen -- a tactic that generally drives more oil accumulation. Using the CRISPR-Cas9 gene-editing technique, the researchers were able to winnow a list of about 20 candidates to a single regulator -- they call it ZnCys -- and then to modulate its expression."

As we've reported, from 2005 to 2012, dozens of companies managed to extract hundreds of millions in cash from VCs in hopes of ultimately extracting fuel oil from algae.

The promise of algae is tantalizing. Some algal species contain up to 40 percent lipids by weight, a figure that could be boosted further through selective breeding and genetic modification. That basic lipid can be converted into diesel, synthetic petroleum, butanol or industrial chemicals.

Today, most of the few surviving algae companies have had no choice but to adopt new business plans that focus on the more expensive algae byproducts such as cosmetic supplements, nutraceuticals, pet food additives, animal feed, pigments and specialty oils. The rest have gone bankrupt or moved on to other markets.

The Exxon-SGI partnership is one of the few remaining algae biofuel efforts.

According to some sources, an acre of algae could yield 5,000 to 10,000 gallons of oil a year, making algae far more productive than soy (50 gallons per acre), rapeseed (110 to 145 gallons), jatropha (175 gallons), palm (650 gallons), or cellulosic ethanol from poplars (2,700 gallons).

The question remains: Can algae be economically cultivated and commercially scaled to make a material contribution to humanity's liquid fuel needs? Can biofuels from algae compete on price with fossil-derived petroleum?

Once capital needs, water availability, energy balance, growing, collecting, drying, and algae's pickiness about light and CO2 are factored in -- the answer, so far, is an emphatic no.

Here's a recently compiled list, by no means complete, of algae companies attempting to pivot away from biofuels.

There are many pieces to the algae puzzle that seem like afterthoughts, but which are actually crucial to the economics -- including co-products, nutrients, harvesting, drying and conversion technology. System design and algae type (which seem to be the focus of this and most discussions) are important, but not the only components.

Considering the immense technical risks and daunting capital costs of building an algae fuel company, it doesnt seem like a reasonable venture capital play. And most -- if not all -- of the VCs Ive spoken with categorize these investments as the longer-term, long-shot bets in their portfolio. But given the size of the liquid fuels market, measured in trillions of dollars, not the customary billions of dollars, it makes some sense to occasionally take the low-percentage shot.

Link:
Genetics Pioneer Craig Venter and Exxon Claim Algae Biofuel Breakthough (Again) - Greentech Media

Researchers at the University of California, Davis, have just reported a small but significant accomplishment: catching the replication of a single DNA molecule on video for the first time. And the footage has revealed some surprising details about this structure on which all life depends.

DNA is composed of two strands bound together in a helical shape, like a twisting ladder. These strands are made of four basesadenine, guanine, cytosine and thymine, abbreviated as A, G, C and T, respectivelystrung together in various patterns and paired in specific ways across the rungs of the ladders. A always pairs with T, and C always pairs with G. Sugar and phosphate molecules help provide architectural support to the ladder-like structure. Human DNA contains about 3 billion bases. Discrete, repeated sequences of bases form the individual genes that encode the instructions for all our working parts. And every time a cell divides, which happens incredibly often, DNA replicates so that each new cell contains a complete copy of our entire genome, or genetic blueprint.

A digital representation of the human genome. Scientists at UC Davis have discovered that DNA replication is not as smooth as they thought. Mario Tama/Getty Images

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The process of DNA replication isa tremendous source of wonder and focus forresearch. The helix must unwind and have each strand copied smoothly and quickly. An enzyme called helicase triggers the unwinding and another called primase initiates the replication process. Athird, called polymerase, travels the length of a strand, adding the requisite base pairs along the way, leaving behind a new strand. Imagine splitting a ladder down the middle and assembling matching halves so that where there was once one ladder now there are two. That is DNA replication, only in place of saws, nails, wood and glue, there are enzymes and many microscopic and complex processes. Mysteries aboundwhen it comes to thishereditary material.

To better probe those mysteries, geneticist and microbiologist Stephen Kowalcyzkowski and colleagues watched DNA from bacteria replicate. They wanted to see exactly how fast the enzymes worked on each strand.

This first-ever view, shown in the video above, revealed a surprise: replication stopped unpredictably and moved at a varying pace. "The speed can vary about 10-fold," Kowalczykowski said in a statement. The two strands also replicated at different speeds.Sometimes the copying stalled on one strand while proceeding on the other. "We've shown that there is no coordination between the strands," said Kowalczykowski. "They are completely autonomous." The process, the researchers report in their study, published in Cell, is much more random than previously suspected.

The three enzymeshelicase, primase and polymeraseare also not alwys in sync. Even if polymerase stops its replication work, helicase can keep unzipping the helix. That lack of coordination leaves the half-helix of DNA exposed and vulnerable to damage. Such exposure is known to trigger repair mechanisms within the cell. Errors in replicating DNA, while often corrected, can also result ingenetic abnormalities that in turn lead to diseases.

This new look at DNA transforms the scientific understanding about replication. "It's a real paradigm shift," saidKowalcyzkowski, "and undermines a great deal of what's in the textbooks."

Continued here:
DNA Replication Filmed for First Time Shows How Awkward and Random Genetics Is - Newsweek

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.

Light can be used as an accurate method to control gene expression, shows groundbreaking optogenetics study by University of Colorado, Duke University and University of Helsinki researchers.

Researchers at the University of Alberta have developed a new method of controlling biology at the cellular level using light.

Rice University bioengineers who specialize in creating tools for synthetic biology have unveiled the latest version of their "biofunction generator and "bioscilloscope," an optogenetic platform that uses light to activate ...

A team of researchers at Cincinnati Children's Hospital Medical Center has developed an antibody that could prevent Candida infections that often afflict hospitalized patients who receive central lines.

A bacterial pathogen can communicate with yeast to block the development of drug-resistant yeast infections, say Irish scientists writing in the May issue of Microbiology. The research could be a step towards new strategies ...

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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