New Science paper from the Skach Lab sheds light on protein folding

The Skach Lab taking a deserved break.

A recent paper published in Science may change how we think about how protein folding in its endogenous context.  For the past 50 years, the principles by which proteins unfold and refold have been studied largely using purified recombinant substrates.  Under these experimental conditions, however, it has been extraordinarily difficult to examine how a protein folds in its native environment.  To address this question, the Skach Lab developed a novel technique that uses fluorescence resonance energy transfer (FRET) to show that folding events are carefully choreographed during synthesis in the cell. Some events are actively delayed, while others are enhanced.  These findings show that the final structure of proteins is precisely tuned by cellular machinery–and more importantly, they challenge almost 50 years of basic dogma, setting the stage to examine folding in a more holistic manner that takes into account environmental factors.

These findings have important health implications. Surprisingly large numbers of rare diseases are caused by inherited mutations that disrupt protein folding.  One example is cystic fibrosis, a lethal disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.  About 70% of those with cystic fibrosis harbor a 3 base pair deletion that results in CFTR misfolding and premature degradation.  Kim and colleagues provide the first detailed analysis of how this region of CFTR actually folds–and they also show that a critical step in the pathway can occur only while the nascent protein is being synthesized and attached to the ribosome. CFTR folding is also linked to the rate of protein synthesis, which is in turn controlled by mRNA codon usage and the availability of specific transfer RNAs.  Thus, they show that both folding and misfolding are integrated into a wide cellular context, not only in disease but also in normal function.

These results have implications for a broad spectrum of disease, ranging from cystic fibrosis to Parkinsons disease, Alzheimer’s disease, prion diseases, hypercholesterolemia, and more, all of which are characterized by protein folding disorders. Beyond the implications for these basic disease pathways, these findings also provide foundational insight into an entirely new class of drugs such as those that act by correcting the underlying defects in the folding of CFTR.

The paper, “Translational tuning optimizes nascent protein folding in cells”, was published in Science on April 24, 2015. The authors are Soo Jung Kim, Jae Seok Yoon, Hideki Shishido, Zhongying Yang, LeeAnn Rooney, Jose Barral, and William Skach, professor of biochemistry, OHSU School of Medicine and VP for Research Affairs, Cystic Fibrosis Foundation.

NIGMS wants to hear from you!

The National Institute of General Medical Sciences examining innovative ways to best support biomedical researchers. Last week we reported on NIGMS’s new funding mechanism for early-career scientists and now they’re seeking input on how best to foster technology development for the research community. More specifically, the Institute is asking for information on the need for development of technologies and the relationship of technology development to other biomedical research. Of particular interest are ideas about:

  • The value of coupling technology development to addressing a significant research question
  • Important factors to consider in peer review of technology development applications
  • Important factors to consider in evaluation of technology development projects and programs
  • The role of industrial or other partnerships in developing technologies to meet future research needs
  • The role of NIGMS in supporting technology development at various stages: exploration, application, optimization, validation and maturation or “hardening”

Let your voices be heard on ideas related to emerging technology concepts, ideas on how to develop these ideas into tools, and how to integrate these tools into your research. This an opportunity to have your own work and that of OHSU drive new NIGMS initiatives.

Career Awards for Medical Scientists: internal deadline July 1

The Burroughs-Wellcome Fund Career Awards for Medical Scientists provides up to $700,000 in support over five years to help physician-scientists bridge their advanced postdoctoral/fellowship training with the early years of faculty service. Proposals must be in the area of basic biomedical, disease-oriented, or translational research.  Proposals in health services research or involving large-scale clinical trials are not eligible. The foundation will make up to two additional awards to clinically trained psychiatrists who focus on research at the interface between neuroscience and psychiatry.

Eligibility:
The ideal candidate will be two years away from becoming an independent investigator, have at least two years or more of postdoctoral research experience, and have a significant publication record. Candidates must hold a Ph.D. as well as an M.D. or D.D.S. degree and received it within the last 10 years. Those who hold a junior faculty appointment may be eligible if they have been in a faculty position for two years or less at the time of application. See sponsor announcement for complete eligibility details.

Limited submission guidelines apply. OHSU may nominate up to five candidates. If you are interested in applying, please submit a brief research summary, CV, and letter of support here by July 1, 2015. The Letter of Intent/Nomination deadline is Aug. 5 and full applications are due to Burroughs-Wellcome by November 12, 2015.

Feel free to email funding@ohsu.edu for questions.

Take a look at this week’s other Funding Opportunities.

Michael Cohen, Ph.D., named Pew Scholar

Michael Cohen, Ph.D.

Hot off last week’s Industry Spotlight comes more news about Michael Cohen: he has been named to the 2015 class of Pew Scholars. The Pew Scholars are selected each year by the Pew Charitable Trusts–the program supports the research of young investigators who demonstrate exceptional potential in biomedical research.  This important award reflects Cohen’s promise as a researcher and innovator. His research concerns how ADP-ribosyltransferases affect learning, memory, and other brain functions. He is engineering these enzymes to identify their protein targets. You can read more about his research here.

 

NRSA Application Workshop: Technical Components, June 30

If you’re planning to apply for a pre- or post-doctoral NRSA fellowship from the NIH in the near future, we encourage you to attend this workshop to learn about essential, non-research elements of your fellowship application. Topics covered include elements needed for an InfoEd proposal, how to develop a budget, how to manage reference letters, biosketches and PMCID numbers,and elements of a great training plan.

This workshop is led by Johanna Colgrove, M.D., Ph.D., program coordinator; Jerry Robertson, grants and contracts administrator; and Rachel Dresbeck, Ph.D., director of research development.

NRSA Application Workshop
Tuesday, June 30, 2015
11 a.m. to 1 p.m. in the Biomedical Research Building 381

Open to both researchers and administrators. Registration now available on Compass.

TTBD Industry Spotlight: Michael Cohen and Takeda Pharmaceuticals

Michael Cohen, Ph.D., assistant professor of physiology and pharmacology

Whether it’s finding an effective vaccine approach to protect against human pathogens, or developing a technology that allows physicians to detect blood vessel abnormalities in the eye, researchers are constantly pushing the boundaries of science to create new, innovative solutions to problems. In the case of Michael Cohen, Ph.D., assistant professor of physiology and pharmacology at OHSU, he is currently working to develop a method to profile new protein synthesis in a cell-specific manner in mice. In order to help move his research forward, he had to seek out additional funding sources.

While searching for alternative resources, Cohen came across a funding alert involving Takeda Pharmaceuticals. Upon reading the program’s description, he felt that his research was the perfect match. Cohen contacted Takeda, and several meetings were held to discuss both parties’ objectives. Ultimately, Takeda agreed to fund his research, thus allowing him to further develop the technology.

When asked about the partnership, Cohen replied, “this is my first experience with industry collaborations, but I have to say, it’s been totally amazing. I don’t feel like there’s any pressure to reach a certain milestone. They just really want to learn about the technology, see where we’re at with it, and give some helpful suggestions.”

Cohen has been working specifically with the New Frontier Science group, a research and development organization within Takeda Pharmaceuticals. This group offers resources to external innovators by providing direct funding, allowing access to drug discovery platforms, and setting up collaborations with expert scientists and engineers within the company. Partnerships with this group are centered on accelerating novel science and developing new technologies.

When asked if he had any advice for other academic researchers considering industry-sponsored research, Cohen replied, “Now that I know it exists, I have been looking for more opportunities because you have to find a way to survive in challenging funding times. And it might take your research in a different direction that you never thought of before.”

Cohen joined OHSU in 2011. He was a postdoctoral fellow at the Weill Cornell Medical College and received his Ph.D. in chemical biology from the University of California in San Francisco. Today, Cohen is still working with Takeda Pharmaceuticals to further develop the technology. His last piece of advice to fellow OHSU researchers? “Just focus on good science. Industry associates will notice, and they’ll like that.”

National Institute of General Medical Sciences announces new funding mechanism for early-career scientists

Earlier this week, NIGMS announced a new funding mechanism for early-career researchers–the MIRA, for Maximizing Investigators’ Research Award for New and Early Stage Investigators (R35). This mechanism is intended to support scientists, rather than specific projects.  It’s a bit of an experiment for NIGMS, so they are limiting eligible applicants to NIH-defined Early Stage Investigators and New Investigators at the assistant professor rank or equivalent (postdocs on K99s are not eligible; but if you have an R00 you may be). This award is an expansion of the funding program released in January for NIGMS-supported investigators with two or more awards from that agency. Unlike the previous award, you don’t need to be already funded by NIGMS to apply.

Your friendly Research News editors heard NIGMS director Jon Lorsch talk about the rationale for this program earlier this spring. We learned that the intention of this program is move away from funding specific projects and instead invest in scientists–for these awards, you don’t even submit an aims page. Lorsch hopes that this approach will improve stability–and therefore creativity–for investigators, as well as allow them to explore promising directions when they arise out of the experiments rather than wait for permission from program officers. NIGMS also hopes they can improve funding distribution and invest in more scientists.  This will allow them to have a broader research portfolio, with more diversity in the kinds of scientists and institutions–something, Lorsch says, that is difficult to achieve in a project-based model under existing funding (read: political) conditions.

Unsurprisingly, there was immediate skepticism about how it would all work (also see comments the NIGMS blog), but give them credit for trying.

Applications are due September 9th (November 19 for AIDS-related applications).

2nd annual NeuroFutures Conference, July 15-17: Register now, abstracts due July 1

One in four U.S. adults suffer from a diagnosable neurological disorder, and a quarter of these are seriously disabled as a result. These patients endure immense physical and emotional suffering, and their family members and caregivers bear a heavy emotional and financial burden. That’s why thought leaders in research, engineering, industry, and clinical settings from around the world will descend on Portland for the 2nd annual NeuroFutures Conference, July 15-17.  Sponsored by the OHSU Brain Institute, the Allen Institute for Brain Science, and the University of Washington, this annual conference explores innovations in neurotechnology.

NeuroFutures Conference
Wednesday, July 15 through Friday, July 17
Sentinel Hotel, 614 S.W. 11th Ave., Portland

Register now.

Topics covered at the conference include:

  • Neuroethics
  • Neuromodulation
  • Metabolic imaging
  • Brain computer interface
  • Big data analytics
  • Tools and techniques
  • Macro imaging
  • Micro imaging
  • Translation barriers

A number of distinguished OHSU experts will present, including Dennis Bourdette, M.D., Kim Burchiel, M.D., Damien Fair, P.A.-C., Ph.D., Jim Galbraith, Ph.D., Kathleen Grant, Ph.D., David Huang, M.D., Ph.D., and Jeff Iliff, Ph.D. For a complete list of speakers and panelists, check the conference website. A full agenda is located on the site, too.

Abstracts are being accepted until July 1. Submission guidelines are here.

Register now!

This conference focuses on the intersection of several fields:  Neuroimaging and brain mapping, the biology underlying healthy and disease state, and neuromodulation to stimulate the nervous system to treat certain neurological diseases. Recent advances illustrate the promise of neurotechnologies–for example, new medical devices have been able to restore hearing to deaf children via cochlear implants, restore vision to a blind person via retinal prostheses, control tremors in Parkinson’s patients via deep brain stimulation, and reduce the frequency and impact of epileptic seizures via neural stimulation. Extending these successes to stroke, Alzheimer’s, traumatic brain injury, depression, and other diseases is the goal.

Bonus opportunity
Haven’t had enough of the brain? NeuroFutures 2015 attendees are invited to attend the Portland International Neuroscience Symposium, also in Portland, July 17-19. Top neuroscience physicians and scientists will address state-of-the-art clinical topics and related research important to neuroscience. Topics include dementia, headache, neuro critical care, terminal care and ethics, and more. For more information, visit the symposium website.

A bird’s eye view of NIH

Sally Rockey

Wondering what NIH leadership really thinks about the future of federal funding for biomedical research? Interested in learning about the impact NIH-funded research is having and the progress that’s been made on large NIH initiatives? Deputy Director for Extramural Research, Sally Rockey, addressed these topics and more in a recent opening plenary presentation at the NIH Regional Seminar on Program Funding and Grants Administration in Baltimore. The full 55 minute presentation, View of NIH from 10,000 feet, is available for viewing here, but following are some highlights:

Impact:

  • 10 percent of NIH’s budget goes toward HIV/AIDS research, an investment that has had a significant impact on the quality and length of patients’ lives. In the mid-1980s, a young person presenting with AIDS had a prognosis of 3 to 6 months to live. HIV research and resulting therapies have given patients diagnosed this year a life expectancy of 70+ years .
  • Cancer rates are declining at the rate of 1 percent per year due to early detection and better treatments.
  • Cardiovascular disease deaths are down over 60 percent in the last half century.
  • Human Genome Sequencing is close to being performed at a cost of $1,000. This compared to the $2 billion spent on the Human Genome Project in the early 1990s.

Funding
NIH’s budget has been essentially flat since 2003, and yet inflation demands larger awards be made to cover research costs. As a result, fewer awards can be made, and success rates have dropped from over 30 percent prior to 2003 to about 18 percent in 2014 .

“Too much good science is being left on the table,” asserts Rockey, so the Office of Extramural Research is advocating for a slow yet predictable trajectory for budget growth rather than continued cycles of rapid expansion and drastic cuts. The funding practices of the past 11 years are “no way to sustain an enterprise,” said Rockey. But she’s optimistic given what she’s hearing from Congress about growing bi-partisan support for more stable and consistent growth.

Rockey also presented data on international research investment compared to that of the U.S./NIH. The percentage of other countries’ budgets spent on biomedical research is growing significantly, while the U.S.’s is declining. China in particular is making large investments in both infrastructure and workforce: between 2007 and 2012, China’s compound annual growth rate of biomedical R&D expenditures was over 32 percent, while the U.S. showed a negative 1.9 percent growth rate.

Read more…

IRB Brown Bag Special Series: eIRB Upgrade Demo

IRB Brown BageIRB Upgrade: Demo

Presented by: Kelly Kidner, IRB analyst

Thursday, June 11
10 to 11 a.m.
OHSU Hospital, 8th floor auditorium

Are you involved with Human Subjects research? Come to the eIRB Upgrade Demo! During this brown bag we will be giving an overall demonstration of the new eIRB system. You can see a presentation of the new Initial Submissions process, the modifications and CRQs and the new Reportable New Information (RNI) system. This brown bag session will be open for questions and answers.

Welcome to the Research News Blog

Welcome to the Research News Blog

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