Monthly Archives: July 2017

The levels of one gene in particular may play a key role in protecting from depression or accelerating its severity, according to a new study from researchers at the University of Maryland School of Medicine.

Depression, which affects over 300 million people,changing the waythey interact with the world, is the mostcommon cause of disabilityglobally.

The study, published Thursday in the Journal of Neuroscience, pinpoints the importance of the levels of gene Slc6a15, which works in neurons of the brain involved with the brains reward system. The levels of this gene, which acts as a neutral amino acid transporterin brain neurons, could affect peoples mood, according to Dr. Mary Kay Lobo, the senior author of the study and an assistant professor in the department of anatomy and neurobiology at the University of Maryland School of Medicine.

The study focused on vulnerable neurons, or parts of the brain that react to stress. While previous studies had indicated Slc6a15 was associated with depression susceptibility, Lobo and her team wanted to examine how levels of this particular gene would correlate with mediating susceptibility to stress.

In their research, the team found that mice who had been genetically modified to have lower levels of the gene were found to exhibit depression-like outcomes after experiencing stress. In mice they had modified to enhance the level of the gene, they found a resilient response to stress, according to Lobo.

They also found that the level of gene Slc6a15 was reduced in the post-mortem analysis of individuals who had suffered from depression.

If we can find ways to actually enhance levels of this molecule in this particular vulnerable neuron population that would be a way to combat depression, Lobo said. This is also a druggable target.

Put more simply, the study of this previously understudied gene could be critical in advancing the understanding of depression and its underlying causes, according to Dr. A.J. Robison, a professor of physiology at Michigan State University who was not involved in the study.

In order to improve, we really need to understand not only how the disease is happening and what went wrong to cause depression, but how the drugs work to combat it, Robison said.This study should lead to a continuing body of work that can really make genuine progress in understanding how depression works and maybe even in treating it.

For Lobo, the next steps entail identifying more of these types of genes and their impact.

We have to go in and find these vulnerable neuron subtypes, perhaps to alleviate depression-like symptoms, she said.

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Researchers Identify Levels Of Gene That Could Play A Key Role In Depression - HuffPost

Recently, a kerfuffle in the world of CRISPR illustrated just how easily moneyand our perception of itcan impact science.

In late May, a paper came out questioning how effective the gene-editing technology really is. Working with mice, researchers found that edits made with CRISPR can also result in thousands of unintended changes to a genome. The study cast serious doubt on whether CRISPR is ready for prime time.

The fallout was swift. Stock prices of three CRISPR companiesEditas Medicine, Intellia Therapeutics and CRISPR Therapeuticstumbled. Scientists affiliated with those companies fired back, questioning the studys methodology. Stocks bounced back. The scientific world was set atwitter, questioning not only the validity of the initial study, but how to trust a rebuttal against that study when it came from those who stood to lose the most from its publication.

Conflicts of interest arent a new problem in science. One frequently-cited example is the role that tobacco industry-funded scientists played in distorting the health consequences of smoking. There is a significant body of evidence suggesting financial interests can correlate with favorable results. But, conflicts of interest arent always all bad. Research funding from sources with a vested interest in a topic can sometimes help advance science that otherwise might not get funded at allthink the patient advocacy groups funding cures for little-known diseases.

Whats undoubtedly true is that money plays a significant role in science. And rarely has there been as much money at stake as with CRISPR, the nascent gene-editing technique that promises to cure everything from genetic disease to global famine by allowing researchers to easily cut and paste particular genes. When scientists whose fortune and reputation hinges on a particular technology speak out against a paper questioning that technology, its hard not to wonder how that bias might factor in.

There is this unspoken assumption the people in academia are driven primarily by the quest for knowledge and the science, Josephine Johnston, a bioethicist at The Hastings Institute, told Gizmodo. But in recent history, controversies over things like tobacco and GMOs have begun to erode that perception. When it became clear that more and more scientists have a specific financial stake, it caused a lot of concern, Johnston said.

When it comes to CRISPR, the financial stakes are certainly complicated. Two separate groups of scientists have long been embroiled in a battle over the patent for the technology, with one headquartered at The Broad Institute of MIT and Harvard, and the other at U.C. Berkeley (so far, the US has awarded the patent to Broad but Europe and China have sided with Berkeley). The patent gives the scientists the ability to license the technology. In this case, Broad has licensed the technology to Editas, a company founded by scientists at both Berkeley and Broad. Berkeley licensed its patents Intellia, which Berkeleys Jennifer Doudna is also a founder of, as well as to CRISPR Therapeutics.

Most of the headline-grabbing scientists associated with CRISPR have major financial stakes in publicly traded CRISPR companies, creating a strong incentive across the industry for CRISPR to succeed. The concern is that a CRISPR-favoring bias could potentially cause researchers to misinterpret or skew study results, or forge ahead with human clinical trials before CRISPR is really ready.

Thats not to say that theres necessarily anything wrong with the points industry-affiliated CRISPR scientists raised in their rebuttal to the paper questioning their science. In fact, several other scientists raised similar concerns.

Finances certainly can influence science. Not just companies, but also the premises supporting government grant finances, George Church, an author of the rebuttal paper and founder of Editas, told Gizmodo via email. We were basically raising issues that the original authors can address. This, fortunately, doesnt require perfect unbiased authors. Anyone can point out a potential problem.

Michael Kalichman, director of UC San Diegos research ethics program, pointed out that financial interest isnt the only bias that scientists have to be wary of.

Weve talked about conflicts of interest for many years in science and for many reasons much of that focus has been on financial conflicts. For one, its easy to see, he told Gizmodo. What I find astonishing is that even scientists forget that there are other conflicts that can influence work, like tenure, your reputation or just being excited about an idea.

Kalichman said his biggest concern is less that scientists are actually doing anything unethical, and more that financial conflicts of interest create the perception that they are. The paper that sparked the CRISPR controversy received press in most major news outlets, and the blowback against it has received significant attention, too.

Part of me is worried about the way [this CRISPR fight] is playing out because of the picture it paints of science, he said. We have this battle going on in the pages of scientific journals that creates this perception that this is what science is about when most of science is not about this.

Johnston echoed those concerns.

The introduction of these financial interests muddies the water enough that people dont know who to trust, she said. Whether or not we can see anything wrong with either study, or anyone else can, theres still this suspicion that the financial stakes must have played some role here. Thats a very corrosive thing across science.

In the initial Nature Methods paper, scientists from Stanford and University of Iowa working to cure blindness in mice found that while CRISPR did successfully edit the gene for blindness, it also caused mutations in more than a thousand unrelated genes. The consequences of those off-target effects, far more extensive than previously realized, are largely unknown. This finding warns that CRISPR technology must be further tailored, particularly before it is used for human gene therapy, the researchers wrote.

As mentioned, scientists associated with CRISPR companies were not the only ones, or even the first, to criticize the studys design. Many scientists raised red flags about basic mistakes, such as misidentifying genes, mislabeling genetic defects, and the small number of animals the researchers had included in their research. But other scientists found the reaction against the paper, was written as a brief letter to the editor intended mainly to point to an area where more study might be needed, to be overwrought. Some, like UC Davis professor Paul Knoepfler, suggested the real problem was that the results had been over-interpreted and blown up in the press, setting in motion an out-sized blowback.

Scientists from Intellia and Editas both sent separate letters to Nature Methods, forcing it to eventually add a note to the study about the controversy surrounding the letter. Whats more, in publishing their own study taking down the initial works methodology, scientists associated with Editas opted to publish a pre-print online before it was peer-reviewed, though the initial paper did go through a peer review process. And while the response paper mentions the institutions and companies each author is affiliated with, there is no clear conflict of interest section. (Church said conflicts of interest will be included with journal publication.)

This week, a pre-print of a second paper published by scientists at Intellia that reanalyzed the original papers data and found far fewer off-target edits also appeared online.

In a statement, the Broad Institute said that the peer review process should weed out the impact of any conflict.

Scientific paperswhether making a new claim, or analyzing an existing scientific claimshould always be subject to rigorous evaluation by the scientific community to establish whether the scientific evidence actually supports the argument in the paper, the Broad Institute told Gizmodo. Such review by the community provides protection against incorrect arguments, whether due to a scientific error, financial or reputational interest, or something else.

Most journals and research institutions have a comprehensive conflict of interest policy. In 2010, UNESCO called for journals to adopt a common standard of dealing with the complex and growing financial arrangements that have developed in recent years between vested interests and independent scientists. Even so, sometimes those ties wind up omitted.

Kalichman said more might be needed to address conflicts of interest in the realm of basic science.

In clinical research, you do everything you can to separate financial interests from the people doing the work, Kalichman said. We dont really talk about that in basic research, but maybe we need to do something like that. Maybe if you have a financial interest, youre not the one that looks at the raw data.

Its next to impossible to fully weed out conflict in sciencebe it financial or otherwise. Besides, it makes sense that scientists should be able to make money off of their own work. But its also impossible not to acknowledge that those interests can influence the science. How could they not?

Update: This story has been updated to include mention of the Intellia study.

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Gene Editing Controversy Reminds Us Just How Much Money Influences Science - Gizmodo

July 6, 2017 Credit: CC0 Public Domain

Globally, depression affects more than 300 million people annually. Nearly 800,000 die from suicide every yearit is the second-leading cause of death among people between the ages of 15 to 29. Beyond that, depression destroys quality for life for tens of millions of patients and their families. Although environmental factors play a role in many cases of depression, genetics are also crucially important.

Now, a new study by researchers at the University of Maryland School of Medicine (UM SOM) has pinpointed how one particular gene plays a central roleeither protecting from stress or triggering a downward spiral, depending on its level of activity.

The study, published today in the Journal of Neuroscience, is the first to illuminate in detail how this particular gene, which is known as Slc6a15, works in a kind of neuron that plays a key role in depression. The study found the link in both animals and humans.

"This study really shines a light on how levels of this gene in these neurons affects mood," said the senior author of the study, Mary Kay Lobo, an assistant professor in the Department of Anatomy and Neurobiology. "It suggests that people with altered levels of this gene in certain brain regions may have a much higher risk for depression and other emotional disorders related to stress."

In 2006, Dr. Lobo and her colleagues found that the Slc6a15 gene was more common among specific neurons in the brain. They recently demonstrated that these neurons were important in depression. Since this gene was recently implicated in depression by other researchers, her lab decided to investigate its role in these specific neurons. In this latest study, she and her team focused on a part of the brain called the nucleus accumbens. This region plays a central role in the brain's "reward circuit." When you eat a delicious meal, have sex, drink alcohol, or have any other kind of enjoyable experience, neurons in the nucleus accumbens are activated, letting you know that the experience is pushing the proper buttons. In depression, any kind of enjoyment becomes difficult or impossible; this symptom is known as anhedonia, which in Latin means the inability to experience pleasure.

The researchers focused on a subset of neurons in the nucleus accumbens called D2 neurons. These neurons respond to the neurotransmitter dopamine, which plays a central role in the reward circuit.

They studied mice susceptible to depression; when subjected to social stressexposure to larger, more aggressive micethey tend to withdraw and exhibit behavior that indicates depression, such as social withdrawal and lack of interest in food that they normally enjoy. Dr. Lobo found that when these animals were subjected to chronic social stress, levels of the Slc6a15 gene in the D2 neurons of the nucleus accumbens was markedly reduced.

The researchers also studied mice in which the gene had been reduced in D2 neurons. When those mice were subjected to stress, they also exhibited signs of depression. Conversely, when the researchers enhanced Slc6a15 levels in D2 neurons, the mice showed a resilient response to stress.

Next, Dr. Lobo looked at the brains of humans who had a history of major depression and who had committed suicide. In the nucleus accumbens of these brains, the gene was reduced. This indicates that the link between gene and behavior extends from mice to humans.

It is not clear exactly how Slc6a15 works in the brain. Dr. Lobo says it may work by altering neurotransmitter levels in the brain, a theory that has some evidence from other studies. She says her research could eventually lead to targeted therapies focused on Slc6a15 as a new way to treat depression.

Explore further: Brain protein influences how the brain manages stress; suggests new model of depression

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Here and throughout the article, shouldn't it say the Slc6a15 gene was expressed more? The wording used makes it sound like these brain cells have more of the gene than other cells in the body, but if I remember high school biology correctly, that isn't true.

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New study identifies gene that could play key role in depression - Medical Xpress

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Tumor gene testing urged to tell if drug targets your cancer Lexington Herald Leader The government has recently approved the first cancer therapy that's based on a tumor's genetics instead of the body part the cancer struck first. Now thousands of patients whose cancer is growing worse despite standard treatment can try this new ... and more »

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Tumor gene testing urged to tell if drug targets your cancer - Lexington Herald Leader

In Brief Researchers have developed a new gene cloning technique that works on thousands of genes at once: the LASSO probe. The tool will enable far more rapid discovery of biomarkers for numerous diseases and new treatments for them. LASSO Cloning

Scientists from Harvard Medical School, Johns Hopkins, Rutgers, and the University of Trento in Italy have developed LASSO cloning, a new molecular technique. LASSO cloning can be used to simultaneously isolate long DNA sequences faster than was previously possible. This new technique speeds up protein creation, which means that genes (the final product of the process) are arrived at more quickly. This, in turn, can enable far more rapid discovery of biomarkers for numerous diseases and their treatments.

In the past, researchers have sussed out what a gene does by cloning its DNA and then expressing the protein it codes for single gene by single gene. With this novel molecular approach, a single reaction can clone and express thousands of DNA sequences at once. The technique involves the use of a novel captured DNA strand, the LASSO probe (Long Adapter Single-Stranded Oligonucleotide). Researchers can use collections of these tools to grab DNA sequences theyre after. Unlike a cowboy roping cattle, however, scientists using the LASSO probe can capture thousands of sequences in a single try.

The LASSO technique improves on molecular inversion probes (MIPs), an older method which is limited to capturing only about 200 DNA bases at once. This is minuscule compared to each LASSO target gene sequence which can be as much as a few thousand DNA base pairs longaround the length of a typical genes protein-coding sequence.

The team used LASSO probes to simultaneously capture more than 3,000 DNA fragments from the E. coli genome as part of a proof-of-concept study. They captured at least 75 percent of their gene targets successfully. More importantly, however, the tool allows researchers to capture sequences in a way that allows them to analyze what the corresponding proteins do.

Were very excited about all the potential applications for LASSO cloning, Larman said in the release. Our hope is that by greatly expanding the number of proteins that can be expressed and screened in parallel, the road to interesting biology and new therapeutic biomolecules will be dramatically shortened for many researchers.

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Powerful New Cloning Technique Can Clone Thousands of Genes at Once - Futurism