Kavli Blog

Program for BRAIN Initiative K99/R00 Career Transition Award to Promote Diversity announces funding opportunities and webinar.

NIH is proud to release a pair of funding opportunity announcements (PAR-18-813 and PAR-18-814) for the BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00) program. The purpose of this program is to enhance workforce diversity in neuroscience and maintain a strong cohort of new and talented, NIH-supported, independent investigators from diverse backgrounds in BRAIN Initiative research areas. This program is designed to facilitate a timely transition of outstanding postdoctoral researchers with a research and/or clinical doctorate degree from mentored, postdoctoral research positions to independent, tenure-track or equivalent faculty positions. The program will provide independent NIH research support during this transition in order to help awardees to launch competitive, independent research careers.

Applicants must have no more than 5 years of postdoctoral research experience at the time of the initial or the subsequent resubmission application. Eligible individuals for this program will be U.S. citizens or permanent residents who fall in one of the categories defined in the Notice of NIH’s Interest in Diversity. Women have been shown to be underrepresented in doctorate-granting research institutions at senior faculty levels in most biomedical-relevant disciplines by the National Science Foundation. For the purposes of these funding opportunity announcements, we consider women underrepresented in the disciplines pertinent to the BRAIN Initiative (underrepresented in the neurosciences/biomedical sciences). PAR-18-813 is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary study to an existing trial, as part of their research and career development. PAR-18-814 is designed specifically for applicants proposing research that does not involve leading a clinical trial, a clinical trial feasibility study, or ancillary clinical trial. The first due date is August 1, 2018, and standard dates apply after that.

NIH is hosting a pre-application webinar on Tuesday, June 12, 2018, from 1:00-2:00PM (EDT) to assist participants in putting together their application. Please register here!

Two re-issued Requests for Applications (RFAs) support innovative methodologically-integrated approaches and multi-PI, team science exploratory approaches within a broader suite of RFAs on brain circuits and integrated approaches.

The NIH Institutes and Centers participating in the BRAIN Initiative are happy to announce two re-issued RFAs that support research on targeted circuit projects and exploratory team-research circuit programs. These RFAs sit within a larger family of funding mechanisms that collectively seek to address long-standing neuroscience issues through an integrated experimental approach, as outlined in the BRAIN 2025 report.

RFA-NS-18-030 (Targeted Brain Circuits Projects) utilizes an R01 mechanism and supports research projects utilizing methodologically-integrated approaches to understand how circuit activity gives rise to mental experience and behavior. These targeted Brain Circuit Project awards will support individual laboratories or small multi-PD/PI groups. The RFA seeks proposals that reflect the NIH BRAIN Initiative interests in the application of cutting-edge methodologies for understanding brain circuit function at cellular and sub-second levels of resolution in ethologically relevant behaviors. Applications should offer specific, feasible research goals as endpoints within a 5-year term. Individual budget requests are not limited but must reflect project needs. The next receipt date is July 3, 2018. Subsequent upcoming receipt dates are: November 6, 2018; July 3, 2019; November 6, 2019; July 1, 2020; November 10, 2020.

RFA-NS-18-029 (Exploratory Team-Research BRAIN Circuit Programs) utilizes a U01 mechanism and will support multi-PI, interdisciplinary team science programs to establish overarching principles of circuit function. This RFA seeks applications that build teams of experts for exploratory studies that integrate theory and modeling with new and emerging methods for recording and manipulating neural circuits across multiple brain regions. Funded projects are expected to elucidate a specific behavioral or neural system in terms of dynamic circuit activity. Successful exploratory studies may lead to subsequent, competing applications for support of multi-component, team-research projects (RFA-NS-17-018). Individual budget requests are not limited but must reflect project needs. The upcoming receipt dates are July 23, 2018 and June 10, 2019.

These RFAs sit within a family of funding opportunities that emphasize the use of cutting-edge methods for activation and recording to understand the behavior of circuits at cellular and sub-second levels of spatial and temporal resolution; that is, at the level of functional units of circuits. For more information about the goals and scope of work for these funding opportunities, please visit our list of active funding opportunities, or contact the BRAIN Team for Integrative and Quantitative Neuroscience.

New administrative supplements integrate neuroethics perspectives and approaches into existing BRAIN Initiative awards.

The NIH Institutes and Centers participating in the BRAIN Initiative are pleased to announce support for administrative supplements to embed ethicists into BRAIN Initiative supported research. Over the course of the last several years, NIH has issued a variety of funding opportunity announcements to support projects that develop and apply technologies towards understanding neural circuit function. As a result, the BRAIN portfolio of awards represents diverse approaches focused on better understanding the fundamental biology of nervous system function. Importantly, the BRAIN 2025 report highlights that this scientific research must be of the utmost value to the public it intends to serve.

The NIH is therefore encouraging applications to PA-18-591 to incorporate neuroethics perspectives and approaches into existing BRAIN Initiative awards. Supplement applications are encouraged from ongoing BRAIN Initiative projects that can readily incorporate core ethical issues associated with research focused on the human brain and also projects developing emerging technologies and advancements in research and development supported by the BRAIN Initiative. The intent of this administrative supplement is to support efforts that would be both complementary and integrative with the transformative, breakthrough neuroscience discoveries supported through the BRAIN Initiative.

As an administrative supplement, the proposal must be within the scope of the research that is already supported. Research proposed in supplement applications should have clear relevance to the BRAIN Initiative. The proposed work may cover pilot projects, resource development, or personnel costs for embedding neuroethics into the research project. Individual requests can be no more than $100,000 in direct costs and may be for one year only. Requests must be received by June 15, 2018 for funding in fiscal year 2018.

Congress recently passed a budget bill that promises increased funding above fiscal year 2017 to NIH, including significant increases for the BRAIN Initiative. The legislation delivers further to support NIH’s mission of conducting biomedical research that will save lives, lead to new drug and device development, reduce health care costs, and improve the lives of all Americans.

On March 23, 2018, President Trump signed the Omnibus Appropriations Bill that provides $37.1 billion for NIH, an increase of $3 billion (or 8.8%) above fiscal year 2017. Thus, for the second consecutive year, NIH has seen funding increases from Congress, indicating strong support for the NIH mission.

The spending bill includes $496 million of appropriated funds authorized in the 21st Century Cures Act. The Cures Act, signed into law in December 2016, allocates funding to NIH each year through 2026, for a total of $4.8 billion. The BRAIN Initiative was one of four highly innovative scientific initiatives designated to receive multi-year funding through the Innovation Fund of the Cures Act, reflecting enthusiasm for the Initiative and its goals. This funding must be appropriated each year by Congress.

In fiscal year 2017, Congress appropriated $250 million to support the BRAIN Initiative, with an additional $10 million coming from the Cures Act Innovation Fund. In fiscal year 2018, Congress has provided an additional $140 million, of which $86 million is from the Cures Act Innovation Fund. This legislation reflects strong bipartisan Congressional support for biomedical research, and will provide NIH with the resources needed to continue to work towards the goals outlined in BRAIN’s strategic plan, the BRAIN 2025 report. The funding will help accelerate BRAIN’s mission to develop and apply innovative tools and neurotechnologies, as well as to support researchers as they seek new ways to treat, cure, and even prevent brain disorders.

In addition to the increased funds for the BRAIN Initiative, the Omnibus Bill increases funding by $414 million, to a total of $1.8 billion in fiscal year 2018, for Alzheimer’s disease research. The bill also includes $250 million for targeted research related to opioid addiction, development of opioid alternatives, and pain management (see also the recent NINDS call for applications directed at the treatment of pain). The agreement expects that NIH will continue its focus on emerging investigators, with actions to significantly reduce the average age of NIH-supported new investigators and support an increase in the number of Ruth L. Kirschstein National Research Service Awards.

The spending bill will fund the government until the end of the current fiscal year.

Miniaturized carbon fiber electrode arrays for intra-nerve recording and stimulation… Reliable measurement and imaging of brain bioenergetics… Emerging medical imaging tool with superior contrast and sensitivity… Improved method for synaptic neural circuit tracing…

Advances in electrode array fabrication improve longevity of nervous system implants

Recent advances in neuromodulation have shown that chronic stimulation of the peripheral autonomic nervous system can be used to treat disease. However, the implants providing this stimulation typically have poor longevity. The electrode size (centimeter-scale) and stiffness, as well as the degree of tissue tolerance for the material, leads to insertion trauma and reactive tissue response. To address these issues, at Boston University, Dr. Timothy J. Gardner and colleagues have developed a method for assembling carbon fiber ultra-micro electrodes on a flexible substrate. They used 3D-printing and laser writing to precisely align the individual fibers and added indium (a malleable metal) to form robust contacts between the fine fibers and the electrical contacts, enabling further miniaturization of the device. These flexible carbon fiber ultra-micro electrodes have low tissue reactivity, and the small size allows many electrodes to be implanted within a small, limited-access area. Further, the carbon fiber stiffness permits easy penetration of biological tissue, including fine peripheral nerves, making it possible to make high-quality intra-nerve recordings at unprecedentedly small scales. A thin layer of iridium oxide was also electrodeposited on the carbon fiber tips, making the arrays usable for intra-nerve stimulation as well as recording. To test the arrays, the researchers conducted an acute in vivo preparation of a small peripheral nerve (125μm diameter, containing ~1000 axons) in anesthetized songbirds and recorded spontaneous multi-unit activity. When they stimulated the nerve using the carbon fiber array, they found that gradually increasing the stimulation intensity produced a graded evoked response. Although histology and long-term experiments have yet to be performed with these electrodes, the size, stiffness, and material suggest improved longevity over current implants. The promise of this technological advance – reducing tissue reactivity while still miniaturizing the electrode implants – holds great potential towards improving bio-electronic therapy.

Carbon fiber array (bottom) implanted in the tracheosyringeal nerve (horizontal white band). The fire-sharpened carbon fibers easily penetrated the intact epineurium sheath. Scale bar: 300μm.

 

A novel magnetic resonance spectroscopy design concept enables simultaneous assessment of phosphorus metabolism in two human brain regions

Many neurological disorders involve a behavioral and cognitive impairment that links to dysfunction in distinct brain regions, including metabolic dysfunction. While phosphorus-31 magnetic resonance (MR) spectroscopy represents a non-invasive, in vivo tool for researchers to assess metabolic impairments in different brain regions, the technology has been limited by certain deficiencies. Specifically, most MR scanners have had difficulty in obtaining simultaneous and high-quality phosphorus-31 signals from multiple brain regions, and low detection sensitivity has limited the signal-to-noise ratio and resolution. To address these technical shortcomings, Dr. Wei Chen and colleagues, at the University of Minnesota, have demonstrated a new dual-coil MR spectroscopy approach that provides simultaneous assessment of phosphorus-31-containing metabolites from two distinct human brain regions of interest. Their novel design enabled them to actively switch the nuclear radiofrequency (RF) transmitter–receiver between two phosphorus-31 RF coils (more than two coils is also feasible), enabling interleaved acquisition of two phosphorus metabolite signals, each from a different area of the brain. The team successfully collected data from human occipital and frontal lobes, simultaneously. This method, the concept of which can be used for other MR applications, may be capable of assessing bio-energetic abnormalities in target brain regions with high detection sensitivity and spectral resolution. The technology could provide insights into the normal function of the brain, as well as improve diagnosis and treatment of neurological disorders.

Representative in vivo phosphorus‐31 three‐dimensional chemical shift imaging (CSI) data detected in the human occipital lobe, as well as maps of phosphorus metabolite signals (phosphocreatine (PCr) and γ‐adenosine triphosphate (γ‐ATP)) overlaid on the anatomical images. (A) Location of the coil placed near the occipital lobe. (B–D) Phosphorus-31 MR spectroscopy (MRS) profiles from three selected CSI slices. (E) Single-voxel phosphorus-31 spectrum denoted by the yellow circle in (C) shows excellent detection sensitivity. (F–H) Corresponding PCr maps. (I–K) Corresponding γ-ATP maps. Similar images were obtained simultaneously from the frontal lobe.

A new imaging technique capable of monitoring the healing process in traumatic brain injury

In the United States alone, there are approximately 2.5 million emergency visits for traumatic brain injury (TBI) every year, but quickly identifying the severity of injury remains a challenge. Currently-used subjective methods and imaging-based modalities are appropriate for diagnosing severe TBI injuries, but many mild-to-medium grade impacts go un-imaged, undiagnosed, and untreated. At the University of California, Berkeley, Dr. Steven Conolly and colleagues have presented data and methods illustrating the ground-breaking non-invasive technology, magnetic particle imaging (MPI). MPI, which uses a different device than magnetic resonance imaging, images a distribution of superparamagnetic iron oxide (SPIO) nanoparticles (a safe tracer) with excellent contrast and sensitivity, anywhere in the body. MPI has no radiation, offers high resolution, and the nanoparticles can be tracked for long periods of time in both the blood and inside cells. Furthermore, because the nanoparticles stay inside the vasculature, only blood appears in the resulting image. With no signal from background tissue, MPI can yield an impressive contrast-to-noise ratio. Conolly’s team demonstrated MPI’s ability to detect internal hemorrhaging in a closed-head TBI rat model. They acquired MPI images that showed SPIO nanoparticles had accumulated rapidly at the impact site and persisted for two weeks. The signal half-life in the impact region was approximately four days, while no signal was detected in the same area of the control animal. The scientific potential of this finding suggests that MPI could eventually improve the diagnosis of internal bleeding for patients suffering from trauma.

(Left) Maximum intensity projection (MIP) of control and TBI animals. Note the large hemorrhage in the TBI animal. (Right) MIP of the animals after 3 days; blue circle represents the impact site, green circles indicate lymph nodes. The TBI rat continues to have significant signal from the hemorrhage and inside the lymph nodes, unlike the control.

A second-generation rabies viral vector is non-toxic to host neurons and enables long-term study of neural circuits

The use of genetically-modified rabies viral (RV) vectors, in labeling neurons and their synaptic connections, has enhanced the study of neural circuit organization. However, their use has been limited to short-term experiments because the virus replicates copiously inside infected neurons, consequently killing them approximately two weeks after infection. At the Massachusetts Institute of Technology and the Allen Institute for Brain Science, Dr. Ian Wickersham and colleagues have introduced a methodology for eliminating the toxicity of RV vectors by using the virus as a retrograde vector and monosynaptic tracer. In the original method, the only viral gene deleted was that which encodes a vital protein within the virus’ outer covering, thus stopping the virus from spreading to other cells but not from replicating within its host cell. Wickersham’s team engineered a new class of RV vector, with a second gene deleted: the gene encoding the viral polymerase, an essential enzyme for viral gene transcription as well as for replication of the viral genome. Therefore, the new version of the virus does not replicate after infecting the cell, leaving infected cells alive and healthy for much longer. In addition, the new virus has been modified to express a DNA recombinase, which is capable (even at low levels) of deleting specific DNA sequences of interest within the infected neuron’s genome. As a result, instead of relying on the virus to, for example, express a fluorescent labeling protein and then proliferate to reach a suitable level of detectability, the new virus triggers its host cell to detectibly express the label. The team injected the new virus into chosen regions within the brains of mice. Among infected neurons, electrophysiological properties in the amygdala were normal after two months, and structural and functional imaging in the cortex appeared normal after four months. This new approach may transform how researchers are able to study the organization and connectivity of the brain.

Example two-photon structural images of the same volume of mouse cortex labeled by the new class of RV vector, at two different imaging time points. Every neuron visible at 4 weeks is still alive and structurally normal at 8 weeks. Scale bar, 100μm.

New BRAIN Initiative K99/R00 Career Transition award to promote diversity, women, and individuals from diverse backgrounds.

NINDS, along with the other NIH Institutes and Centers participating in the BRAIN Initiative, is happy to announce the BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00). As highlighted in the BRAIN 2025 report, supporting biomedical research workforce diversity is critical towards training the next generation of investigators. This K99/R00 program is intended for individuals from diverse backgrounds (including nationally underrepresented groups) who are working in research areas supported by the BRAIN Initiative.

In particular, this notice is particularly targeted towards eligible U.S. citizens or permanent residents who fall in one of the categories defined in the Notice of NIH’s Interest in Diversity. Women have been shown to be underrepresented in doctorate-granting research institutions at senior faculty levels in most biomedical-relevant disciplines by the National Science Foundation and would be considered as eligible candidates for this diversity program.

Applicants would require at least 12 months of mentored research training and career development (K99 phase) before transitioning to the independent research (R00) phase of the program. Full details of the Funding Opportunity Announcement are expected to be published in April 2018 on the NIH BRAIN Initiative site, as well as in the NIH Guide, with an anticipated application due date in June 2018.

In a recent interagency program solicitation, the National Science Foundation (NSF) announced funding opportunities for the Smart and Connected Health (SCH) program. Related to the SCH program, the National Institute of Neurological Disorders and Stroke (NINDS) is soliciting applications directed at the treatment of pain.

Representing the collaboration of NSF, a partner in the BRAIN Initiative, and the NIH, the newly announced SCH: Connecting Data, People, and Systems program (NSF-18-541) aims to address the need for integration between the computing, informatics, and engineering disciplines within the biobehavioral medical research community. The SCH program will support fundamental research towards substantial transformations in public health, medicine, and healthcare. NSF expects that this fundamental research, and the development of new tools and methods across many dimensions, will effectively connect data, people, and systems, collectively and significantly benefiting the health of the country. Collaborations between academia, industry, and other organizations are strongly encouraged, to establish better linkages between fundamental science, medicine, healthcare, and technology development, deployment, and use. Proposed work must make fundamental contributions to two or more disciplines (e.g., computer or information sciences, engineering, social, behavioral, cognitive, and/or economic sciences), and address a key health problem.

NINDS has recently released a notice (NOT-NS-18-052) soliciting applications directed at the treatment of pain. NINDS would like to accelerate the development of devices for the treatment of pain. The notice refers to several funding opportunity announcements, including the NSF-NIH SCH program and the BRAIN Initiative: Next Generation Invasive Devices Recording and Modulation in the Human Central Nervous System (RFA-NS-18-021, RFA-NS-18-022, RFA-NS-18-023). For the SCH program, NINDS is interested in applications for next-generation multidisciplinary science that encourages research in pain in a variety of areas of value to health, such as networking, pervasive computing, advanced analytics, sensor integration, privacy and security, modeling of socio-behavioral and cognitive processes and system and process modeling.

Only integrative proposals involving well-coordinated, multi-disciplinary teams will be considered in response to the SCH program solicitation. Subject to the availability of funds, an estimated 8 to 16 projects per year will be funded. Projects awarded in fiscal year 2018 will be funded for up to a four-year period and for up to a total of $300,000 per year. Investigators interested in taking advantage of this opportunity, which has a proposal deadline of May 22, 2018 (and December 11, annually thereafter), are encouraged to contact a Program Officer listed on the program website. This program solicitation has a proposal deadline of May 22, 2018 (and December 11, annually thereafter).

The meeting will convene BRAIN Initiative awardees, staff, and leadership from contributing federal agencies, plus representatives and investigators from participating non-federal organizations, and members of the media, public, and Congress. This open meeting provides a forum for discussing exciting scientific developments and potential new directions, and to identify areas for collaboration and research coordination.

We are gearing up for the 4th annual BRAIN Initiative Investigators meeting, which will be taking place from April 9-11 at the Bethesda North Marriott Hotel and Conference Center in Rockville, MD, just outside of Washington, DC. Over the course of three days, the meeting will feature a welcome from NIH Director Dr. Francis Collins, plenary addresses (speakers: Dr. Bill Newsome, Dr. Doris Tsao, Dr. Tom Sudhof, Dr. Huda Zoghbi), research highlight talks, and poster sessions on new scientific advances stemming from the U.S. BRAIN Initiative. Additional assorted and focused sessions will convene subgroups to discuss the various exciting efforts taking place throughout the BRAIN Initiative, including international neuroscience efforts.

To learn more about this meeting and previous BRAIN PI Meetings, visit the BRAIN Initiative Alliance website at www.braininitiative.org/events/pimeeting.

Registration closes on Tuesday, March 20th, so register today here! If you are planning on attending, please tell us about it on Twitter by using the hashtag: #studyBRAIN. We look forward to seeing you there!