Category Archives: Molecular Genetics

Q&A

Penn's Kiran Musunuru talks to us about the technology that has been both praised and criticized for its ability to alter human DNA and potentially cure disease.

Kiran Musunuru is an associate professor of medicine in genetics in the Perelman School of Medicine at the University of Pennsylvania. / Courtesy

CRISPR, the technology being used to edit genes in humans, remains polarizing. On one end, detractors argue that using the technology for certain purposes, like performing gene editing on embryos, is not only dangerous but unethical. On the other end, proponents say CRISPR has the potential to revolutionize human health, and early data shows they might be right. Despite a medical community that is still split on the issue, researchers in the U.S. are kicking tests of the technology into high gear. Several clinical trials have launched in the U.S. testing CRISPRs ability to treat various diseases.

NextHealth PHL spoke with Kiran Musunuru, an associate professor of medicine in genetics at the Perelman School of Medicine at the University of Pennsylvania about the true potential of CRISPR technology and how we can expect it to evolve in the future.

NextHealth PHL: What exactly is CRISPR?Musunru: CRISPR is sort of a catch-all term that covers a variety of technologies. If youre saying CRISPR, youre referring to a broad set of tools that may do it in different ways but are all intended to do a form of gene editing or genome editing.

How do basic CRISPR technologies work?The simplest form of CRISPR, what I call version 1.0, is the original standard CRISPR that most laboratories and companies interested in developing new therapies use. It is a two-component system. There is a protein and an RNA molecule thats about 100 bases in length. The protein and the RNA molecule come together to create what well call a molecular machine and the purpose of this molecular machine is to scan across any DNA molecule it encounters. So if you put the CRISPR-Cas9 into the nucleus of a human cell, this molecular machine will scan the entire genome.

The machine has two key functions built into it; the first is a GPS function. When you change the first 20 bases in a DNA length (the first 20 bases is basically the address) to whatever address you want, the GPS function makes the machine go through the entire genome and find the sequence that matches the address. The second function of this machine is to protect the genome, like a search-and-destroy function. You put in the address, it goes to that matching place in the genome and then it makes a cut in the DNA.

Cutting the DNA is actually a bad thing but the cells have ways to try to fix that break, and the actual editing is a result of the cell trying to fix that break in the DNA, not from CRISPR itself, interestingly enough.

How does CRISPR turn a break in someones DNA into a good thing?There are a few ways this can happen. The safest thing you can do is to break a gene or turn off a gene. The metaphor I like to use is to think of the whole genome as a book, and each chromosome in the genome is a chapter in the book, and each gene is a paragraph in the chapter. Together, it all has a meaning. But lets say you had to turn off a gene, the equivalent of making that break in the DNA would be like tearing the page through that paragraph. So, the simplest thing the cell can do and will try to do is to simply tape that tear back up. But as you can imagine, sometimes you tape it back up and its fine, the paragraph is still legible and the meaning is still there, and it eventually heals and functions like it did before. But in this case, thats actually not what you want. The outcome that you want with CRISPR is that you actually want to turn off the gene, not to rip it and make it the way it was before.

What has to happen is when you make the tear, the tear is so rough, you get those jagged edges and you try to tape it up but it doesnt quite fit, the letters dont quite match up. You tape it up as best as you can but its illegible, some letters are lost, and the meaning of the paragraph is lost. Thats exactly what happens with gene editing, the cell tries to repair that break in the DNA, doesnt get it quite right, and loses some bases and that messes up the gene and turns it off.

However, in this scenario, you cant really control what happens. All you can hope for is that that tear you make is going to mess up the gene and thats okay if all youre trying to do is turn it off. Most of the trials underway now are about turning off the gene, and theyre all taking advantage of the fact that its relatively easy to mess up genes and turn off genes. Just like tearing a page its crude, but its effective.

Theres CRISPR 1.0, this first generation of the technology thats not very precise and is a bit arduous. What are the newest forms of CRISPR and how are they better than earlier versions of the technology? There is a newer form of the technology called base editing that keeps the GPS function intact but removes the cutting function. In place of the cutting function, it attaches another machine onto CRISPR and makes chemical modifications in certain areas. This version of CRISPR is more like a search and replace. CRISPR provides the search but then another machine attached to it is doing the replacing. With base editing you can make more precise changes, but only rarely will it make exactly the type of change you want.

The latest form of CRISPR is called prime editing, and we still dont have a good sense of how well it works because its so new. Whats tantalizing is that it looks like it can turn CRISPR into a precise word processor or an eraser that allows you to erase a letter and put in a new letter. CRISPR is very much a wave of technology, and as it gets better, its going to allow us to do more and more powerful things.

There are some extreme ideas about what CRISPR can do. Some believe scientists can use the technology to alter hair or eye color or give patients superhuman athletic or intellectual abilities. Is any of this possible with CRISPR?It depends on what traits youre talking about changing. Since eye color and hair color are controlled by single genes, you could possibly make a single gene change with CRISPR. The problem is, how do you get CRISPR to go where it needs to go to change your hair or eye color? How do you get it into all your hair follicles or through all the cells in your eye? It might be a simpler change to make, but it might not be easy to do in a live adult. Scientists have now edited human embryos, resulting in live-born people. Theres been a lot of ethical debate about whether thats a good thing. If you want to change something like hair color in a single cell embryo made through in-vitro fertilization, thats a bit different and might not be as difficult.

There are some very complicated things, like intelligence or athletic ability, that are not going to be easy to change. Youd probably have to change hundreds of genes, and thats not going to happen anytime soon. With CRISPR as it is now, maybe you can change one gene; maybe if you really work at it you can change two genes, but hundreds of genes? Youre not going to be able to do that with CRISPR anytime soon.

What has CRISPR been used to treat so far and what could it be used for in the future?There are multiple trials underway to treat rare liver disorders. More recently CRISPR has been used in clinical trials at Penn where at least three patients have been dosed using CAR T immunotherapy. In this case, theyre trying to make patients cells more effective at fighting cancer. But again, that editing is being done outside the body.

There are some things that seem like they would be difficult to treat, but if its the right type of disease and you can get CRISPR to where you need it to go, it might work. One example is in sickle cell disease. The cells that you need to fix in sickle cell disease are in the bone marrow. Fortunately, bone marrow is relatively straight forward to work with. You take the cells out and edit them with some form of CRISPR outside of the body and then put them back in.

Something like cystic fibrosis would be much harder because it affects the entire surface of potentially multiple organs inside the body. Its much harder to deliver CRISPR to all of those places in the body.

There are two other clinical trials that have started in the U.S. One is from a company called CRISPR Therapeutics to treat sickle cell disease and similar blood disorders. Theres another trial underway to treat a genetic form of blindness and this editing would actually happen inside the body.

Originally posted here:
Q&A: Everything You Need to Know About the Future of CRISPR-Cas9 - Philadelphia magazine

SEATTLE--(BUSINESS WIRE)--Shape Therapeutics, Inc. (ShapeTx), a development-stage biotechnology company leading the field of RNA-editing gene therapy, announces $35.5M in Series A financing, led by New Enterprise Associates (NEA), with additional participation from CureDuchenne Ventures. The new capital will enable the company to extend its growing portfolio of intellectual property, recruit and hire top scientific talent and advance its groundbreaking RNA and protein targeting platforms focused on curing human diseases.

These platforms include the proprietary ShapeTx RNAfix technology that enables direct in vivo targeting and modification of RNA by leveraging proteins such as Adenosine Deaminases Acting on RNA (ADARs), suppressor tRNAs, and engineered adeno-associated viruses (AAVs). The RNAfix platform differentiates from other contemporary genome engineering technologies by engaging natural human cellular machinery to modify RNA.

ShapeTx was founded on the work of Dr. Prashant Mali, Assistant Professor of Bioengineering at UCSD, who during his postdoctoral fellowship in the George Church laboratory at Harvard Medical School pioneered the use of CRISPR in human cells. ShapeTx RNAfix platform is built upon his lab's most recent work demonstrating in vivo use of guide RNAs to recruit native ADARs and to fix mutations in multiple rare genetic disease mouse models.

Our technology can correct mutations or target specific genes in neurodegenerative, oncology, metabolic and rare genetic disorders by hijacking naturally occurring proteins such as ADARs present in our cells using just a short guide RNA. Our proprietary new platform avoids the risk of in vivo immunogenicity and permanent off-target damages commonly associated with CRISPR-based approaches, explained Francois Vigneault, Ph.D., President and CEO, who was previously VP of Research at Juno Therapeutics after a successful co-acquisition of AbVitro, Inc. by Juno and Celgene.

Ed Mathers, Partner at NEA and Board member at ShapeTx, said, One rarely comes across a proprietary technology platform with such transformative potential led by a focused and data-driven scientific group with a successful track record in pre-clinical and clinical development. The team has shown us an exciting demonstration of the technology in multiple in vivo models, alongside one of the strongest IP estates we have seen in the field. NEA looks forward to backing the company in future rounds as they move the technology toward the clinic.

While the ShapeTx platform will be enabling for many other genetic diseases, Dr. Malis in vivo proof of concept in Duchenne Muscular Dystrophy was quite exciting and could potentially lead to a cure for families suffering from such a debilitating disorder, said Debra Miller, CEO and Founder of CureDuchenne and CureDuchenne Ventures.

The ShapeTx Series A financing coincides with the formation of a world-class Scientific Advisory Board comprised of foremost global experts in genomics, bioengineering, and gene editing, including George Church Ph.D., James Collins Ph.D., and Don Cleveland Ph.D. The scientific advisory board will serve as strategic advisors and ensure that the research and development of its platforms meet the highest standards of scientific merit.

Prashant and Francois are some of the most innovative and brilliant individuals that have come through my lab over the years, and it will be impressive to see these two disrupt the field of gene therapy with this paradigm-shifting technology, said Dr. George Church, Professor in Genetics at Harvard Medical School and member of the ShapeTx Scientific Advisory board.

Shape Therapeutics Scientific Advisory Board Members:

George Church, Ph.D.

George Church Ph.D., world-famous geneticist, molecular engineer, and chemist. He developed the methods used for the first genome sequence & million-fold cost reductions since, as well as pioneered many of the CRISPR advances in genome editing. He is currently a Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and the Massachusetts Institute of Technology (MIT). He is Director of the U.S. Department of Energy Technology Center and Director of the National Institutes of Health Center of Excellence in Genomic Science. He has received numerous awards, including the 2011 Bower Award and Prize for Achievement in Science from the Franklin Institute and election to the National Academy of Sciences and Engineering.

James Collins, Ph.D.

James Collins Ph.D., is one of the pioneers of the field of synthetic biology and has made multiple synthetic biology and bioengineering breakthroughs in biotechnology and biomedicine. He serves as the Termeer Professor of Medical Engineering & Science and Professor of Biological Engineering at MIT, as well as a member of the Harvard-MIT Health Sciences & Technology Faculty, and core member of the Wyss Institute. His many awards include a Rhodes Scholarship, a MacArthur Genius Award, a National Institutes of Health Directors Pioneer Award. Jim is also an elected member of the National Academy of Sciences, the National Academy of Engineering, the National Academy of Medicine, the American Academy of Arts & Sciences, as well as a charter fellow of the National Academy of Inventors.

Don Cleveland Ph.D.

Don Cleveland Ph.D. is an award-winning inventor and pioneer in the field of Antisense Oligonucleotide (ASO) and their uses in gene therapy. He was recently awarded the Breakthrough Prize in Life Sciences for his work on the pathogenesis of disease and ASO-mediated treatment approaches in ALS and Huntingtons disease. Don is currently Professor of Medicine and Department Chair of Cellular and Molecular Medicine and Neurosciences at the University of California at San Diego, and Head, Laboratory for Cell Biology at the San Diego branch of Ludwig Cancer Research. He has made pioneering discoveries on the mechanisms of chromosome movement and cell-cycle control during normal cellular division, as well as the principles of neuronal cell development and the relationship to defects that contribute to inherited neurodegenerative disease.

About Shape Therapeutics, Inc.

Shape Therapeutics, Inc. is creating the worlds leading RNA and protein targeting platforms focused on the cure of human diseases. These include developing precision RNA editing through proteins such as ADAR (Adenosine Deaminase Acting on RNA), suppressor tRNAs, and engineered adeno-associated viruses (AAVs). The RNAfix technology allows for the editing of RNA using natural human cellular machinery, limiting the risk associated with immunogenicity, cellular toxicity, or off-target DNA editing. The teams founders include Prashant Mali, Ph.D., Francois Vigneault, Ph.D., and John Suliman. ShapeTx is headquartered in Seattle, Washington, with a satellite site opening in Cambridge, Massachusetts. For additional information, visit http://www.ShapeTx.com.

About NEA

New Enterprise Associates, Inc. (NEA) is a global venture capital firm focused on helping entrepreneurs build transformational businesses across multiple stages, sectors, and geographies. With more than $20 billion in cumulative committed capital since the firm's founding in 1978, NEA invests in technology and healthcare companies at all stages in a company's lifecycle, from seed stage through IPO. The firm's long track record of successful investing includes more than 225 portfolio company IPOs and more than 375 acquisitions. For additional information, visit http://www.nea.com.

About CureDuchenne Ventures

CureDuchenne Ventures supports Duchenne research by using philanthropic donations to encourage the development of new Duchenne drugs. Through an impact financing model, we can provide equity or royalty financing to biotech and pharmaceutical companies. CureDuchennes portfolio includes 16 wide-ranging projects with several successful exits. Investments from CureDuchenne Ventures have successfully de-risked and leveraged more than $2.3 billion in follow-on financing from venture capital, biotech, and pharmaceutical companies to fund emerging projects to find treatments for Duchenne. For additional information, visit https://www.cureduchenne.org/ventures/.

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Shape Therapeutics, Inc. Raises $35.5M Series A Financing, Led by NEA and Announces the Formation of a World-Class Scientific Advisory Board, to...

STILLWATER, Okla. Udaya DeSilva doesnt remember exactly how he wound up in the hospital. He lost at least 45 minutes on the evening of Oct. 14 when he was struck by a pickup while riding his bike.

The Oklahoma State University professor of animal molecular genetics was wrapping up a 10-mile ride and was only a mile from home.

He remembers starting to go up the hill on Lakeview Road as it crosses Boomer Lake. The next thing he knew, he was waking up in Stillwater Medical Centers emergency department.

He says considering the situation, thats probably for the best.

Now 17 days later, hes about to go home. But hes still got a long road to travel before hes back to normal.

DeSilva is going home in a back brace and using a walker after suffering a compression fracture in his back, a dislocated hip, a separated shoulder, a fracture in his right hand, a Grade 3 concussion and superficial injuries all the way down his right side. He says he lost about four units of blood.

Hes facing months of recovery and physical therapy.

But in spite of the extent of his injuries, DeSilva feels fortunate. The picture would probably have been different if he hadnt been wearing his helmet.

All of this is going to take time, but its 100% fixable, he said. If I was not wearing a helmet, I would be dead.

He bases that conclusion on the amount of damage the back of his helmet sustained.

DeSilva expects to make a full recovery and to eventually be back on his bike. Its something he grew up doing in Sri Lanka and has continued to do through his 30 years in the U.S.

He spends a lot of time on a bike, using it to commute to work work most days.

There were a few times he says it seemed like drivers got a little too close, but he doesnt usually feel unsafe on the road. He had one experience where a driver screamed at him.

DeSilva says that Stillwater has become much more bike-friendly in the past 10 years. But there is obviously room for improvement.

Multiple witnesses said the driver who struck him failed to provide at least three feet of clearance around his bike as state law requires.

Although the accident report notes that as a contributing factor, it doesnt indicate that the driver received a citation. An inquiry to the Stillwater Police Department about it hadnt received a response by press time.

DeSilva is a believer in having the proper safety equipment, now more than ever.

You take precautions, you do whatever you can, but things like this happen, he said. One thing I want people to know is: Wear a helmet.

Oklahome Bike Laws

Under Oklahoma Title 47, motorists are required to allow at least three feet of space between their vehicle and a bicycle they are passing or overtaking.

The penalty for violating that law, if it results in a collision causing serious physical injury, is a fine of up to $500.

If the collision causes the death of another person, the fine rises to $1,000, in addition to other penalties prescribed by law.

Bicycles are considered vehicles under Oklahoma law. They have the right to travel on the roadway, even if they cant travel as fast as other traffic.

They are only allowed to ride two abreast and should ride single file on roads divided into lanes.

If a usable bike path is provided, local ordinances can require bicyclist to ride on that path instead of the road.

Bicycles traveling slower than the normal speed of traffic must ride as close as possible to the right-hand curb unless they are passing, turning left or avoiding objects and hazards.

Front and rear lights and reflectors are required while on streets or highways with a speed limit over 25 miles per hour.

By the Numbers:

The NHTSA overview report for 2018 shows that fatalities for occupants of every type of motorized vehicle except large trucks decreased from 2017 to 2018. Fatalities for nonoccupant pedestrians and cyclists increased during that same period.

A reported 857 cyclists died in 2018, a 6.3% increase and the highest number since 1990.

Charles writes for Stillwater News Press, a CNHI News Service publication.

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OSU professor injured in bike wreck feels lucky to be alive - Norman Transcript

SALT LAKE CITY, Oct. 28, 2019 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, today announced that it will present results from seven studies at the 2019 National Society of Genetic Counselors (NSGC) annual meeting being held Nov. 58, 2019 in Salt Lake City.

"We are excited to present new data from seven studies at this years NSGC meeting," said Susan Manley, MS, CGC, MBA, senior vice president of Medical Services at Myriad Genetics. Our presentations highlight the companys commitment to advancing precision medicine in oncology and womens health.

A list of presentations at 2019 NSGC is below. Please visit Myriad Genetics at booth #711 to learn more about our leading portfolio of precision medicine products. Follow Myriad on Twitter via @myriadgenetics and follow meeting news by using the hashtag #NSGC19.

myRiskHereditaryCancer

ForesightCarrierScreen

AishwaryaArjunan

PrequelTMPrenatalScreen

About Myriad myRisk Hereditary CancerThe Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

AboutForesight Carrier ScreenThe Myriad Foresight Carrier Screen is designed to maximize detection of at-risk couples for serious, prevalent, and clinically-actionable conditions. Foresight has a rigorous disease selection that focuses on 175+ conditions that provides meaningful information to patients. Additionally, Foresight offers superior technology with unmatched detection rates for the vast majority of genes on the panel (>99% across ethnicities) which means patients can trust both positive and negative results.

About PrequelTM Prenatal ScreenThe Myriad Prequel Prenatal Screen is a noninvasive prenatal screen that uses cell-free DNA (cfDNA) to determine if a pregnancy is at an increased risk for chromosome abnormalities, such as Down syndrome. Prequel has been shown to be superior to screening methods that use maternal age, ultrasound and serum screening. Additionally, Prequel has a lower false-positive rate and false-negative rate than these other methods. The Prequel Prenatal Screen can be ordered with the Foresight Carrier Screen and offered to all women, including those with high body mass index, and ovum donor or a twin pregnancy.

About Myriad GeneticsMyriad Genetics Inc. is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice HRD, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to data being presented for its genetic tests at the 2019 National Society of Genetic Counselors Meeting being held Nov. 58, 2019 in Salt Lake City; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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Myriad Genetics to Present Seven Studies at the 2019 National Society of Genetic Counselors Annual Meeting - BioSpace

A university committee is seeking comments as part of a regular performance review of Vice President for Finance Tim Walsh. Reviews of senior administrators are typically conducted in the fourth year of a five-year term, and the results complied in a confidential report.

This will be the second such review for Walsh, who has served in his current post since 2011.

Executive Vice President Tallman Trask asked Peter Feaver, professor of Political Science, to chair the committee. Other members are: Kerry Abrams (School of Law); Billy Newton (School of Medicine); Scott Greenwood (Duke University Alumni Association); Joanna Rojas (Office of Audit, Risk and Compliance); Beth Sullivan (Professor of Molecular Genetics and Microbiology); and Laura Meyer Wellman (Board of Trustees).

Walsh joined Duke in 2004 as assistant vice president and controller. In 2011, he was promoted to vice president for finance, where he oversees an array of accounting, reporting and financial functions, including the treasury, budgeting, procurement, real estate, stores and licensing, administrative systems, research costing and compliance, auxiliaries finance and controller's functions.

At Duke, Walsh has, among other things, co-chaired efforts to streamline core financial and administrative processes that support the university's international activities; chaired the Research Administration Continuous Improvement (RACI) initiative, which promotes the efficient and effective administration of Duke's $1.1 billion research enterprise; and overseen the implementation of monthly reporting processes that provide greater transparency of the university's comprehensive financial performance to executive administrators and trustees.

An important part of the review process is the gathering of opinions from the universitys many constituencies. Comments on performance and suggestions for the future are important to the committees work. Communication should include the nature of interactions with Walsh and his team so that the committee can best understand the context of the comments.

The committee will discuss responses and a summary will be included in the written report to the executive vice president. The committee will hold all communication in strict confidence.

Comments should be submitted by Nov. 8, 2019. Please send any communications to:

Peter Feaver, Chair

Walsh Review Committee

Box 90204

Durham, North Carolina 27708

admin-review@duke.edu

Read the rest here:
Comments Sought in Regular Review of Vice President for Finance and Treasurer Tim Walsh - Duke Today

CHARLOTTESVILLE, Va. (CBS19 NEWS) -- Scientists looking for a way to help breast cancer patients have found a new organelle inside cells that may help.

Researchers at the University of Virginia School of Medicine say the organelle works to prevent cancer by ensuring that genetic material is sorted correctly as cells divide and problems with this organelle have been connected to a subset of breast cancer tumors due to a lot of mistakes when segregating chromosomes.

According to a release, this analysis offers a new way for doctors to sort patient tumors as they choose the therapies that may be used to treat the patients.

The researchers hope these insights will help doctors to better personalize treatments to best benefit patients, potentially sparing up to 40 percent of breast cancer patients from treatment that will not be effective.

Some percentage of women get chemotherapy drugs for breast cancer that are not very effective. They are poisoned, in pain and their hair falls out, so if it isn't curing their disease, then that's tragic, said researcher P. Todd Stukenberg, PhD, of the UVA Department of Biochemistry and Molecular Genetics. One of our goals is to develop new tests to determine whether a patient will respond to a chemotherapeutic treatment, so they can find an effective treatment right away.

Stukenberg and his team of researchers ay the organelle they found is essential but ephemeral, as it only forms when needed to ensure chromosomes are sorted correctly. It then disappears when that task is complete.

Stukenberg also compares the organelle to a droplet of liquid that condenses within other liquid, saying the droplets act like mixing bowls that concentrate certain cellular ingredients to allow for biochemical reactions to occur in a specific location.

What's exciting is that cells have this new organelle and certain things will be recruited into it and other things will be excluded, he said. The cells enrich things inside the droplet and, all of a sudden, new biochemical reactions appear only in that location. It's amazing.

He says the organelle acts more like a gel that allows cellular components to come in and exit but it has binding sites that concentrate a small set of the cell's contents.

Our data suggests this concentration of proteins is really important, said Stukenberg. I can get complex biochemical reactions to occur inside a droplet that I've been failing to reconstitute in a test tube for years. This is the secret sauce I've been missing.

The release adds that researchers have known for about eight years that cells make droplets like this for other processes, but they did not know they are made on chromosomes during cell division.

Stukenberg thinks such droplets are common and more important than previously understood, saying the cells are using these non-membranous organelles to regulate much of their work.

The release says this discovery helps scientists better understand the process of mitosis, or cell division, and it sheds light on cancer and how it occurs.

The organelle's main function is to fix mistakes in tiny microtubules that pull apart chromosomes when cells are dividing. They ensure that each cell gets the correct genetic material.

However, in cancer cells, the repair process is defective, and the cancer cells can be driven to be more aggressive.

Stukenberg has also developed tests to measure the amount of chromosome mis-segregation in tumors, which he hopes will allow doctors to pick the proper treatment for patients.

His next step he says will be to examine the strange organelle's role in colorectal cancer.

The findings have been described in the scientific journal Nature Cell Biology.

See original here:
Researchers find new organelle that may help cancer patients - CBS19 News

Amsterdam, the Netherlands, and Holzgerlingen, Germany, October 30, 2019, 10:00 am CET - Curetis N.V. (the "Company" and, together with its subsidiaries, "Curetis"), a developer of next-level molecular diagnostic solutions, today announced that the Curetis Group Companies will be attending several key conferences in the fourth quarter of 2019.

November 2019

EIT Health German-French Bilateral Meeting, November 4-5 2019 Mannheim, Germany (Ares Genetics GmbH) 54th Annual Northeast Branch American Society for Microbiology, November 7-8, 2019 Randolph, MA, USA (Curetis USA Inc.)DICON/DASON Fall 2019 Symposium (Duke Infection Control Outreach Network / Duke Antimicrobial Stewardship Outreach Network), November 8, 2019 Raleigh, NC, USA (Curetis USA Inc.)Southeastern Association of Clinical Microbiology (SEACM) Annual Fall Meeting, November 14-16, 2019 Myrtle Beach, SC, USA (Curetis USA Inc.)DxPx - Diagnostics and Research Tools Partnering Conference, November 18, 2019 Dsseldorf, Germany (Ares Genetics & Curetis GmbH)European Summit of Industrial Biotechnology, November 18-20, 2019 Graz, Austria (Ares Genetics GmbH)Emerging Antimicrobials and Diagnostics in AMR 2019, November 19-20, 2019 Amsterdam, The Netherlands (Ares Genetics GmbH & Curetis GmbH)EPAASM 49th Annual Symposium (Eastern Pennsylvania Branch of the American Society for Microbiology), November 22, 2019 Philadelphia, PA, USA (Curetis USA Inc.)

December 2019

3rd Congress Immunotherapies & Innovations for Infectious Diseases, December 3-4, 2019 Lyon, France (Ares Genetics GmbH)

ASPH Midyear Clinical Meeting (American Society of Health-System Pharmacists), December 8-12, 2019 Las Vegas, NV, USA (Curetis USA Inc., booth #773)

13. Nationaler Qualittskongress Gesundheit, December 12-13, 2019 Berlin, Germany (Ares Genetics GmbH)

###

About Curetis

Curetis N.V.s (CURE.NX) goal is to become a leading provider of innovative solutions for molecular microbiology diagnostics designed to address the global challenge of detecting severe infectious diseases and identifying antibiotic resistances in hospitalized patients.

Curetis Unyvero System is a versatile, fast and highly automated molecular diagnostic platform for easy-to-use, cartridge-based solutions for the comprehensive and rapid detection of pathogens and antimicrobial resistance markers in a range of severe infectious disease indications. Results are available within hours, a process that can take days or even weeks if performed with standard diagnostic procedures, thereby facilitating improved patient outcomes, stringent antibiotic stewardship and health-economic benefits. Unyvero in vitro diagnostic (IVD) products are marketed in Europe, the Middle East, Asia and the U.S.

Curetis wholly owned subsidiary Ares Genetics GmbH offers next-generation solutions for infectious disease diagnostics and therapeutics. The ARES Technology Platform combines what the Company believes to be the most comprehensive database worldwide on the genetics of antimicrobial resistances, ARESdb, with advanced bioinformatics and artificial intelligence.

For further information, please visit http://www.curetis.com and http://www.ares-genetics.com.

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This document constitutes neither an offer to buy nor an offer to subscribe for securities and neither this document nor any part of it should form the basis of any investment decision in Curetis.

The information contained in this press release has been carefully prepared. However, Curetis bears and assumes no liability of whatever kind for the correctness and completeness of the information provided herein. Curetis does not assume an obligation of whatever kind to update or correct information contained in this press release whether as a result of new information, future events or for other reasons.

This press release includes statements that are, or may be deemed to be, forward-looking statements. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms believes, estimates, anticipates, expects, intends, targets, may, will, or should and include statements Curetis makes concerning the intended results of its strategy. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. Curetis actual results may differ materially from those predicted by the forward-looking statements. Curetis undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law.

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Contact details

Curetis Contact DetailsCuretis N.V.Max-Eyth-Str. 4271088 Holzgerlingen, GermanyTel. +49 7031 49195-10pr@curetis.com or ir@curetis.comwww.curetis.com - http://www.unyvero.com

International Media & Investor InquiriesakampionDr. Ludger Wess / Ines-Regina Buth Managing Partnersinfo@akampion.comTel. +49 40 88 16 59 64Tel. +49 30 23 63 27 68

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Originally posted here:
Curetis To Attend Key Conferences in the Fourth Quarter of 2019 - Yahoo Finance

More than 150 New Zealand scientists under 30 have signed a letter to the Green Party urging a rethink of its stance on the regulation of genetic modification. The full text of the letter follows.

To the members and supporters of the Green Party of Aotearoa New Zealand and their representatives in government

Climate change is one of the greatest crises in human history, and our current law severely restricts the development of technologies that could make a vital difference. In 2003 the 1996 Hazardous Substances and New Organisms Act was modified to tightly regulate research into genetic modification (GM). This legislation and the surrounding public debate was driven by uncertainty about the risks that these new technologies posed to biodiversity and human health, and resulted in creating one of the toughest regulatory environments in the world for this field of research.

We, an emerging generation of New Zealand scientists with expertise in and/or undertaking research in the biological sciences*, are writing to request that the Green Party reconsider its position on the regulation of these technologies. We are addressing this letter to the Greens because of a history of leading in science-based policy such as climate action, even when that path is difficult. We believe that GM based research could be decisive in our efforts to reduce New Zealand and global climate emissions as well as partially mitigating some of the impacts of climate change. At the same time, we emphasise that potential reduction of impact is not a substitute for emission reduction.

The period since the introduction of the 2003 legislation has seen important GM related research in the areas of agricultural efficiency, carbon sequestration, and alternative protein production. The existing regulation in New Zealand inhibits application of advances such as these, blocking not only the development of green technology, but the potential for a just transition away from extractive and polluting industries. New Zealand has the opportunity to be a world leader in such a transition: for example, the development and demonstration of effective technologies to reduce agricultural emissions could have an international impact and set an example for other countries.

While such a powerful technology as targeted genetic modification certainly requires controls, existing frameworks do not enable public and environmental benefits from these technologies to be realised. The gene editing expert advice panel supported by The Royal Society Te Aprangi, the Prime Ministers Chief Science Advisor, and the interim climate change committee have recently called for public discussion on potential reform of New Zealands laws around modern gene editing techniques.

As a confidence and supply member of the current government the Greens have the ability to drive this reform: the members can persuade the party to reconsider its policy position, and the Members of Parliament can influence the government it supports to revise the legislation. The Greens have been strong advocates of both climate action and evidence based policy informed by science. In this light we call upon its members, supporters, ministers, and MPs to add their voices to the cause of a science-based approach to climate, on behalf of the people and environment of both Aotearoa and the world.

Ng mihi

PhD

Kyle Webster, University of Auckland, Bio-nanotechnology

Luke Stevenson, Victoria University of Wellington, Biotechnology

Emilie Gios, University of Auckland, Microbial ecology

Morgane Merien, University of Auckland, Biological Sciences Entomology

Lucie Jiraska, University of Auckland, Environmental Microbiology

Victor Yim, University of Auckland, Peptide chemistry

Zach McLean, University of Auckland, Genetic engineering

Declan Lafferty, Plant and FoodResearch/University of Auckland, Genetics and Molecular Biology

Samarth Samarth, University of Canterbury, Plant Biology

Juliane Gaviraghi Mussoi, University of Auckland, Avian Behaviour

Alex Noble, University of Canterbury, Biology

Kelsey Burborough, University of Auckland, Genetics

Matthew Mayo-Smith, University of Auckland, Plant Molecular Biology

Moritz Miebach, University of Canterbury, Plant-microbe interactions

Olivia Ogilvie, University of Auckland, Food Biotech / Biochemistry

Rachel Bennie, University of Canterbury, Human Toxicology

Sean Mackay, University of Otago, Chemistry and Nanotechnology

Georgia Carson, Victoria University of Wellington, Cell and Molecular Biology

Ruby Roach, Massey University

Jeremy Stephens, Massey University, Biology

Zidong (Andy) Li, Massey University, Molecular Cancer Biology

Aqfan Jamaluddin, University of Auckland, Molecular Pharmacology

Michael Fairhurst, Victoria University of Wellington, Microbiology

Nikolai Kondratev, Massey University, Plant Biology

Mariana Tarallo, Massey University, Plant pathology

Ellie Bradley, Massey University, Plant pathology

Mercedes Rocafort Ferrer, Massey University, Plant pathology

Yi-Hsuan Tu, Massey University, Biochemistry & Microbiology

Sean Bisset, Massey University, Biochemistry

Patrick Main, Massey University, Biological sciences

Abigail Sharrock, Victoria University of Wellington, Biotechnology

Alvey Little, Victoria University of Wellington, Molecular Microbiology

William Odey, Victoria University of Wellington, Biotechnology

Gabrielle Greig, Victoria University of Wellington, Molecular Microbiology

Melanie Olds, Victoria University of Wellington, Biotechnology

Jennifer Soundy, Victoria University of Wellington, Biological Sciences

Matire Ward, Victoria University of Wellington, Cell and molecular bioscience

Tom Dawes, Victoria University of Wellington, Plant Ecology

Hamish Dunham, Victoria University of Wellington, Biomedical science

Amy Alder, Victoria University of Wellington, Neuroscience

Caitlin Harris, University of Otago, Plant genetics

Lucy Gorman, Victoria University of Wellington, Coral reef biology

Vincent Nowak, Victoria University of Wellington, Biotechnology

Brandon Wright, University of Otago, Biochemistry

Anna Tribe, Victoria University of Wellington, Cancer cell biology

Conor McGuinness, University of Otago, Breast Cancer

Genomics/Immunology Kelsi Hall, Victoria University of Wellington, Biotechnology

Andrew Howard, University of Waikato, Biochemistry

Mitch Ganley, Victoria University of Wellington, Biotechnology/vaccines

Matt Munro, Victoria University of Wellington, Biomedical Science

Prashath Karunaraj, University of Otago, Genetics

Pascale Lubbe, University of Otago, Evolutionary genetics

Mackenzie Lovegrove, University of Otago, Genetics, Insect evolution

Nicholas Foster, University of Otago, Ecology

Taylor Hamlin, University of Otago, Antarctic Marine Ecosystem & Movement Ecology

Fionnuala Murphy, Massey University, Proteomics

Amanda Board, University of Canterbury, Protein Biochemistry

Esther Onguta, Massey University, Food Technology

Nomie Petit, University of Auckland, Proteins

Liam Le Lievre, University of Otago, Plant Reproduction

James Hunter, University of Otago, Ecology

Samarth Kulshrestha, University of Canterbury,

Rebecca Clarke, University of Otago, Whole body regeneration

Sarah Killick, University of Auckland, Environmental Science

Stephanie Workman, University of Otago, Developmental Genetics

Erik Johnson, University of Otago, Oceanography

Declan Lafferty, University of Auckland, Molecular Biology

Laurine van Haastrecht, Victoria University of Wellington, Glaciology

Leo Mercer, Victoria University of Wellington, Environmental Studies

Aidan Joblin-Mills, Victoria University of Wellington, Chemical Genetics

Gabrielle Keeler-May, University of Otago, Marine Science

Aqfan Jamaluddin, University of Auckland, Pharmacology

Spencer McIntyre, University of Auckland, Biological Sciences

Sarah Inwood, University of Otago, Genetics

Isabelle Barrett, University of Canterbury, Freshwater ecology

Olivia Angelin-Bonnet, Massey University, Biostatistics

Hannah McCarthy, Massey University, Plant Pathology

Sofie Pearson, Massey University, Plant Science

Zac Beechey-Gradwell, Lincoln University, Plant physiology

Hannah Lee-Harwood, Victoria University of Wellington, Biotechnology

Euan Russell, University of Otago, Microbiology

Masters

Kelly Styles, University of Auckland, Biological Sciences

Merlyn Robson, University of Auckland, Virology

Andra Popa, University of Auckland

James Love, University of Auckland, Bioinformatics

Evie Mansfield, University of Auckland, Molecular Microbiology

Ash Sargent, University of Auckland, Immunology

Sabrina Cuellar, University of Auckland, Plant Genetics

Renji Jiang, University of Canterbury, Plant pathology

Morgan Tracy, University of Canterbury, Ecology

See the original post here:
GM could be decisive: An open letter to the Green Party from young NZ scientists - The Spinoff

Adding carvedilol, the active compound of a blood pressuremedicine, to enzyme replacement therapy (ERT) for Pompe disease can improve its effectiveness in reaching and strengthening skeletal muscles, a study in mice suggests.

This finding, Evaluation of antihypertensive drugs in combination with enzyme replacement therapy in mice with Pompe disease was published in Molecular Genetics and Metabolism.

At present, enzyme replacement therapy (ERT) is the only effective treatment for Pompe disease, a rare genetic disorder caused by the absence or deficiency of the acid alpha-glucosidase (GAA) enzyme.

When GAA activity is low, a sugar molecule called glycogen accumulates inside cells, damaging organs and tissues throughout the body, but primarily skeletal muscle, smooth muscle, and cardiac muscle. If left untreated, the accumulation of glycogen in cardiac and skeletal muscle leads to severe and progressive muscular weakness, risking heart and respiratory failure.

There is, however, a major limitation in ERT. Skeletal muscle is less accessible to it, meaning the therapy has trouble getting into this type of muscle cell. Skeletal muscles poor response to ERT has been attributed to a serious lack of a protein receptor called cation-independent mannose-6-phosphate receptor (CI-MPR) on its cells.

Animal studies suggest that an active compound common to blood pressure medications (with work to control hypertension) could increase the uptake of ERT by muscle cells, by increasing the amount of muscle (muscle hypertrophy), and therefore the amount of CI-MPR.

Investigators atDuke Universityevaluated the effects of ERT with and without three anti-hypertensive agents: carvedilol, losartan, and propranolol. All these compounds have different ways of working, or mechanisms of action, in the body. They experimented using a mouse model of Pompe disease called the GAA knockout (absent) mouse.

Animals were assigned to one of seven groups: no treatment, ERT alone, ERT with carvedilol, ERT with losartan, ERT with propranolol, or to only losartan or carvedilol. Drugs were given to the mice in drinking water, and one week after treatment initiation, recombinant human GAA was given by injection every week for a month. Five days following the last GAA injection, scientists examined the animals cardiac and muscle function.

The team reported that carvedilol uniquely increased muscle strength, while losartan uniquely decreased heart rate. GAA activity was also found to be significantly higher in the heart following either losartan or propranolol being added to enzyme replacement therapy, compared to mice left untreated as a control group.

Both carvedilol or propranolol significantly increased GAA activity in the animals quadriceps, the muscles in the front of the thigh, compared to control mice. However, only carvedilol administration significantly increased GAA activity in quadriceps, in comparison with ERT alone, the scientists wrote.

These findings indicate that the greatest rise in enzymatic activity occurred in response to carvedilol, the active substance in the blood pressure medication Coreg. Carvedilol is a beta-blocker that relaxes the smooth muscle that makes up blood vessels, leading to an overall reduction in blood pressure.

Because more than half (seven of 13) of the mice given losartan, either alone or in combination with ERT, died during the study, researchers thought this active molecule potentially toxic in Pompe, and suggested physicians should be mindful of it when prescribing high blood pressure medications to Pompe patients.

Currently we demonstrated unique toxicity from the administration of losartan in mice with Pompe disease, the researchers wrote.

Because of the benefits seen in diseased micegiven carvedilol during ERT, they recommended the compound be studied in a clinical trial in patients.

Carvedilol was well-tolerated, and the ability to use a -blocker [beta-blocker] in patients that will not interfere with ERT would be highly valuable for clinical use in patients with Pompe since they often require a -blocker to mitigate disease-associated hypertension, the investigators concluded.

A clinical trial of carvedilol in patients with Pompe disease should be considered to further evaluate its usefulness.

With over three years of experience in the medical communications business, Catarina holds a BSc. in Biomedical Sciences and a MSc. in Neurosciences. Apart from writing, she has been involved in patient-oriented translational and clinical research.

Total Posts: 3

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

Read this article:
ERT to Treat Pompe May Work Better in Combo with Blood Pressure Medication, Study Says - Pompe Disease News

Researchers have identified 57 genetic variations of a gene strongly associated with declines in blood oxygen levels during sleep. Low oxygen levels during sleep are a clinical indicator of the severity of sleep apnea. The study, published today in the American Journal of Human Genetics, was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

A persons average blood oxygen levels during sleep are hereditary, and relatively easy to measure, says study author Susan Redline, MD, senior physician in the Division of Sleep and Circadian Disorders at Brigham and Womens Hospital, and professor at Harvard Medical School, in a release. Studying the genetic basis of this trait can help explain why some people are more susceptible to sleep disordered breathing and its related morbidities.

When we sleep, the oxygen level in our blood drops, due to interruptions in breathing. Lung and sleep disorders tend to decrease those levels further, and dangerously so. But the range of those levels during sleep varies widely between individuals and, researchers suspect, is greatly influenced by genetics.

Despite the key role blood oxygen levels play in health outcomes, the influence of genetics on their variability remains understudied. The current findings contribute to a better understanding, particularly because researchers looked at overnight measurements of oxygen levels. Those provide more variability than daytime levels due to the stresses associated with disordered breathing occurring during sleep.

The researchers analyzed whole genome sequence data from the NHLBIs Trans-Omics for Precision Medicine (TOPMed) program. To strengthen the data, they incorporated results of family-based linkage analysis, a method for mapping genes that carry hereditary traits to their location in the genome. The method uses data from families with several members affected by a particular disorder.

This study highlights the advantage of using family data in searching for rare variants, which is often missed in genome-wide association studies, says James Kiley, PhD, director of the Division of Lung Diseases at NHLBI. It showed that, when guided by family linkage data, whole genome sequence analysis can identify rare variants that signal disease risks, even with a small sample. In this case, the initial discovery was done with fewer than 500 samples.

The newly identified 57 variants of the DLC1 gene were clearly associated with the fluctuation in oxygen levels during sleep. In fact, they explained almost 1% of the variability in the oxygen levels in European Americans, which is relatively high for complex genetic phenotypes, or traits, that are influenced by myriad variants.

Notably, 51 of the 57 genetic variants influence and regulate human lung fibroblast cells, a type of cell producing scar tissue in the lungs, says study author Xiaofeng Zhu, PhD, professor at the Case Western Reserve University School of Medicine. This is important, he said, because Mendelian Randomization analysis, a statistical approach for testing causal relationship between an exposure and an outcome, shows a potential causal relationship between how the DLC1 gene modifies fibroblasts cells and the changes in oxygen levels during sleep.

This relationship, Kiley added, suggests that a shared molecular pathway, or a common mechanism, may be influencing a persons susceptibility to the lack of oxygen caused by sleep disordered breathing and other lung illnesses such as emphysema.

Continued here:
Genetic Study: Shared Molecular Pathway Might Influence Susceptibility to Lack of Oxygen Caused by Sleep-disordered Breathing and Other Lung Illnesses...