Innate immune detection of fungal pathogens Fungal crosstalk with mammalian hosts Mechanisms of fungal persistence/colonization at barrier tissues Cellular mechanisms of antifungal immune response in vivo
NIAID invites research applications to study the critical drivers of tuberculosis (TB) transmission at the individual and population levels in high-burden settings, develop methods to measure transmission rates, and assess potential interventions through the notice of funding opportunity (NOFO) Halting Tuberculosis (TB) Transmission (R01, Clinical Trial Optional).
Research Objectives
The TB transmission cycle is extremely complex with multiple contributing host/pathogen/micro-environmental factors. The key drivers of transmission are not completely understood. Improved knowledge of the interactions and factors driving transmission would allow efficacious approaches for preventing transmission to be developed or improved and adapted for broad scale-up.
NIAID is interested in applications covering the following research areas:
Understanding the impact of the spectrum of TB disease, including the role of asymptomatic, pre-symptomatic, and differentially culturable TB, in transmission.
Aerobiology.
Environmental impacts on transmission.
Understanding nontraditional spread (e.g., without cough or other symptoms, community spread with limited contact).
Development or assessment of new methods or tools to measure transmission.
Defining characteristics or sub-populations of Mycobacterium tuberculosis (Mtb) strains that impact transmission, including the role of Mtb strain heterogeneity.
Studies of transmission in high-risk groups (e.g., healthcare workers, congregate settings).
Studies to understand the impact of HIV co-infection and antiretroviral therapy on transmission of TB.
Studies to understand the impact of comorbidities on TB transmission (e.g., diabetes, malnutrition).
Studies to understand how to most effectively utilize resources to reduce transmission (e.g., preventive therapy, active screening strategies, targeted diagnosis, improved ventilation or airflow patterns).
We will accept low-risk, non-investigational new drug (IND) clinical trials, so long as the trial includes outcomes to improve understanding of drivers of TB transmission.
Nonresponsive Research Areas
NIAID will consider applications including the following research areas to be nonresponsive and not review them:
Zoonotic TB transmission, e.g., TB transmission from animals to humans or animals to animals; animal studies are allowed if they are a readout of human-to-human TB transmission.
Clinical trials that require an IND application.
Projects for development of systemic chemoprophylaxis, host-directed therapeutic agents, or vaccines as potential interventions.
If you are proposing an NIH-defined clinical trial, refer to Research Methods Resources for information on developing statistical methods and study designs.
Award and Deadline Information
NIAID intends to fund four or five awards through this NOFO. Application budgets are not expected to exceed $750,000 in annual direct costs and should reflect the actual needs of the project. The scope of the proposed project should determine the project period, to a maximum of 5 years.
Submit applications by December 4, 2024, at 5 p.m. local time of the applicant organization.
Send any inquiries to Dr. Karen Lacourciere, NIAID’s scientific/research contact, at lacourcierek@niaid.nih.gov or 240-627-3297. Send any peer review related inquiries to Dr. Soheyla Saadi, NIAID’s peer review contact, at saadisoh@nih.gov or 240-669-5178.
Contact Us
Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.
NIH’s fellowship application and review process will change for applications due on or after January 25, 2025. To preview these updates, NIH hosted a webinar titled Revisions to the Fellowship Application and Review Process in September 2024. If you missed it, watch now to get a better sense of the changes that lie ahead.
As background, the Center for Scientific Review Advisory Group recommended updates to the fellowship application and review process that will ensure the most fair, objective, and rigorous process for all applicants. Additionally, these changes are intended to better focus the review process on the needs and goals of the candidate, shorten the application process, and make the process easier to complete.
Continue reading for three takeaways from the recorded event to keep in mind when preparing your next fellowship application.
Follow New Application Format When Resubmitting Your Applications
Remember that the new FORMS-I Application Format will apply to all fellowship applications due on or after January 25, 2025. This includes resubmissions that follow applications that were previously submitted using the current format (FORMS-H). Many of the changes listed below will be included within the updated General PHS Fellowship Supplemental Form. Because of the scope of the changes, you and your sponsor(s) should factor in additional time if updating an application for resubmission.
What Information Should I Provide in my New Application?
The newly structured candidate section, which has replaced the Fellowship Applicant Section, will ask for four personal statements: 1) a statement of professional and fellowship goals, 2) a statement of fellowship qualifications, 3) a self-assessment, and 4) a statement of scientific perspective. The statement of scientific perspective allows candidates to discuss why their chosen field of science is important, the ways in which the research training project will advance the field, broader unresolved questions in the chosen field, and how biomedical research might advance them.
There are also significant changes to the Research Training Plan and Sponsor Commitment, as well as a new Sponsor Commitment Section.
Note as well that fellowship candidates will no longer be required to include their undergraduate or graduate grades in applications submitted on or after January 25, 2025.
Get a Head Start on Preparing Your Applications—No Need to Wait
Although the full instructions for fellowship applications are not available yet, you don’t need to wait to start preparing your applications. As part of the new changes to the fellowship application states, candidates can start working on the following aspects of their application:
Define your research goals.
Design the research training project.
Write your research training project Specific Aims and research project strategy.
Develop your training and mentorship goals and plans.
You may also want to consider discussing your career and fellowship goals with your sponsor(s).
Resources and Other Information
In late January 2025, NIH’s Office of Extramural Research will host an additional fellowship policy webinar for applicants who are new to the process (in advance of the next standard due date on April 8, 2025). Registration information will be forthcoming.
Last month, Dr. Monica M. Bertagnolli took office as the 17thNIH Director, the first surgeon and the second woman to hold that position. In her career as an investigator, she was at the forefront of the field of clinical oncology. Her laboratory focused on advancing understanding of the genetic drivers of gastrointestinal cancer development and the role of inflammation as a promoter of cancer growth.
Her priorities as NIH Director include ensuring clinical trials yield the best results by increasing the diversity of participants; embracing the rapid expansion of new learning-based analytical tools and ensuring their use improves care for all people; and restoring trust in science by making it accessible to all communities and inspiring the next generation of doctors and scientists.
Attend Webinar for DEIA Excellence Supplemental Awards
Prepare Now for Upcoming Opportunity on Systems Modeling
In an October 25, 2023 Guide notice, we announced our intent to publish a funding opportunity to support a Center of Excellence for Systems Modeling of Infection and Immunity Across Biological Scales. The Center will be large—potential applicants should assemble leadership teams with a range of expertise and experience to develop multiple coordinating cores and research projects. If interested, read the notice linked above, then begin planning for meaningful collaborations and projects.
Register for Native American Health Research Webinar on January 25
NIH will host an informational webinar to discuss the Intervention Research to Improve Native American Health (IRINAH) Program on January 25, 2024, at 1 p.m. Eastern Time. The initiative supports etiologic research; research that develops, adapts, or tests interventions for health promotion, prevention, treatment, or recovery; and research on dissemination and implementation. Refer to the November 16, 2023 Guide notice for registration details.
Note that NIAID participates in the IRINAH R01 notice of funding opportunity (NOFO), but not the related R21 or R34 NOFOs.
Monthly Automated Reminders for Rejected Final FFRs
When your grant concludes, you are responsible for submitting a Final Federal Financial Report (FFR) that covers the entire competitive segment and indicates the exact balance of unobligated funds. NIH may reject the submission if there are discrepancies between the federal share of expenditures reported on the Final FFR and the net cash disbursements reported in the Payment Management System (PMS).
Beginning immediately, NIH’s Office of Policy for Extramural Research Administration Closeout Center will send monthly emails to recipients that have Final FFRs in rejected status with instructions to resubmit an acceptable Final FFR in the PMS in a timely manner.
Contact Us
Email us at deaweb@niaid.nih.gov for help navigating NIAID’s grant and contract policies and procedures.
An Aedes mosquito, similar to those studied by Dr. Patricia Scaraffia.
Credit:NIAID
Mosquitoes are considered one of the most dangerous animals on earth because of their broad distribution and the many pathogens they transmit to humans. Some of the most important human diseases in tropical and temperate regions of the planet are caused by mosquito-borne pathogens. Malaria, dengue, and filariasis, among other mosquito-borne diseases, kill or sicken millions of people worldwide every year.
Mosquito-borne pathogens are transmitted to the vertebrate host, such as a human, when the mosquito bites the host in search of blood. The proteins found in blood are essential for female mosquitoes: without it, they lack the resources to create eggs. Greater knowledge of the biological processes involved in the mosquito life cycle could lead to new or improved strategies to control mosquito populations.
Dr. Patricia Scaraffia, Associate Professor at the Tulane University School of Public Health and Tropical Medicine, has dedicated her career to understanding the metabolism of the mosquito Aedes aegypti that carries the pathogens responsible for dengue, Zika, chikungunya, and yellow fever to humans.NIAID reached out to Dr. Scaraffia about her team’s research.
What got you interested in studying mosquito metabolism?
I have studied the metabolism of insects that are vectors of pathogens causing human diseases since I was a graduate student at the Universidad Nacional de Cordoba, in Argentina. My Ph.D. dissertation was focused on the energy metabolism in Triatomine insects, vectors of Trypanosoma cruzi, the etiological agent of Chagas´ disease. After my dissertation, I participated as a speaker in a two-week course for PhD students entitled Biochemistry and molecular biology of insects of importance for public health. During the course, Argentinian professors encouraged me to contact the late Dr. Michael A. Wells, a leader in insect metabolism, and apply for a postdoctoral training in his lab. Soon after, I joined Dr. Wells´s lab at the University of Arizona as a research associate and opened a new line of investigation in his lab. Since then, I have never stopped working on A. aegypti mosquito metabolism. I am passionate and curious about the tremendous complexity of mosquito metabolism. It is a fascinating puzzle to work on. It constantly challenges me and my research team to think outside the box when trying to decipher the unknowns related to mosquito metabolism.
Dr. Patricia Scaraffia's work focuses on the secrets of mosquito metabolism.
Credit:Dr. Patricia Scaraffia
What are the metabolic challenges faced by mosquitoes after feeding on blood?
Female mosquitoes are a very captivating biological system. It is during blood feeding that female mosquitoes can transmit dangerous, and sometimes lethal, pathogens to humans. Interestingly, the blood that the females take could be twice their body weight, which is impressive. Female mosquitoes have evolved efficient mechanisms to digest blood meals, eliminate excess water, absorb and transport nutrients, synthesize new molecules, metabolize excess nitrogen, remove nitrogen waste, and successfully lay eggs within 72 hours! Despite significant progress in understanding how females overcome these metabolic challenges, we have not yet fully elucidated the intricate metabolic pathways, networks, and signaling cascades, nor the molecular and biochemical bases underlying the multiple regulatory mechanisms that may exist in blood-fed female mosquitoes.
What are the greatest potential benefits of understanding mosquito metabolism?
Metabolism is a complicated process that involves the entire set of chemical transformations present in an organism. A metabolic challenge faced by mosquitoes is how to break down ammonia that results from digesting a blood meal and is toxic to the mosquito. With NIAID support, we found that in the absence of a functional metabolic cycle to detoxify ammonia, A. aegypti mosquitoes use specific metabolic pathways that were believed to be non-existent in insects. This discovery has opened a new field of study.
A better understanding of mosquito metabolism and its mechanisms of regulation in A. aegypti and other mosquito species could lead us to the discovery of common and novel metabolic targets and/or metabolic regulators. It would also provide a strong foundation for the development and implementation of more effective biological, chemical and/or genetic strategies to control mosquito populations around the world.
What are the biggest challenges to studying mosquito metabolism?
We have often observed that genetic silencing or knockdown—a technique to prevent or reduce gene expression—of one or more genes encoding specific proteins involved in mosquito nitrogen metabolism results in a variety of unpredictable phenotypes based on our knowledge of vertebrate nitrogen metabolism. Notably, female mosquitoes get control of the deficiency of certain key proteins by downregulating or upregulating one or multiple metabolic pathways simultaneously and at a very high speed. This highlights the tremendous adaptive capacity of blood-fed mosquitoes to avoid deleterious effects and survive.
We have been collaborating closely with scientists that work at the University of Texas MD Anderson Cancer Center Metabolomics Core Facility, and more recently, with bioanalytical chemists that work in the Microbiome Center’s Metabolomics and Proteomics Mass Spectrometry Laboratory in Texas Children’s Hospital in Houston. Our projects are not turn-key type of projects with quick turn-round times. We have to invest considerable time and effort to successfully develop and/or optimize methods before analyzing mosquito samples. Despite these challenges, our research work keeps motivating us to unlock the metabolic mysteries that female mosquitoes hold.
Your research has focused on Aedes aegypti, the main vector of dengue, Zika, etc.Why did you choose to study this mosquito species rather than others that are also important vectors of malaria and other diseases?
My research has focused on Aedes aegypti not only because it is a vector of pathogens that pose public health threats, but also because it is genetically one of the best-characterized insect species. The availability of the Aedes aegypti genome is a great resource for a wide range of investigations. In addition, Aedes aegypti is relatively simple to rear and maintain in the lab. In my lab, we are interested in expanding our metabolic studies to other mosquito species by working in collaboration with scientists with expertise in the biology of different vectors.
What important questions remain unanswered about mosquito metabolism?
Many important questions remain unanswered about mosquito metabolism. I’d like to highlight a few of them that may help us enhance our knowledge of the mosquito as a whole organism rather than as a linear sum of its parts. For example, what are the genetic and biochemical mechanisms that drive metabolic fluxes in mosquitoes in response to internal or external alterations? How do key proteins interact with each other, and how are they post-translationally regulated to maintain mosquito metabolism? How are the metabolic networks regulated in noninfected and pathogen-infected mosquitoes? What are the critical regulatory points within the mosquito metabolism and the vector-host-pathogen interface?
While basic science will continue to be crucial in answering these questions, to successfully fight against mosquitoes, we must work together as part of a multidisciplinary team of scientists to tightly coordinate our efforts and close the gap between basic and applied science.
Postbacs at Rocky Mountain Laboratories presented during a recent in-person session of the NIAID Postbac Research Spotlight Series
Credit:NIAID
By Emily Youngblood, Postbac in the Food Allergy Research Section, Laboratory of Allergic Diseases (LAD)
Want to learn about the research NIAID’s postbaccalaureate (postbac) trainees are conducting? The “NIAID Postbac Research Spotlight Series” is an initiative designed to highlight the work of postbacs and the incredible breadth of research being conducted at NIAID. Postbacs are provided an opportunity to give a 10-minute oral presentation on their research followed by 3 minutes of questions from attendees. The spring sessions of the 2024 Series covered parasite-bacteria relationships, mechanisms behind HIV vaccines, filoviruses, enteroviruses, optimization of lung organoids, and many more fascinating topics.
For postbacs who are nervous about speaking in front of others, participating in the Spotlight Series is a chance to practice in a low-pressure, supportive environment. Worried you don’t have data? You can instead opt to talk about gaps in your research field that you want to fill. Interested in discovering what other postbacs are accomplishing? This is the perfect setting to learn and ask questions! Other benefits include practicing how to talk about your research for interviews or future presentations and meeting other postbacs.
Presenting your research can be a daunting experience, a thorn in the side of many scientists. However, effectively communicating your science is a crucial skill for those interested in a career in research, and the more practice, the better. To that end, the Spotlight Series provides a welcoming environment where you can focus on honing your presentation skills.
“Public speaking in academic [and] research settings can be so stressful, so being able to do so in an environment where everyone is so supportive and thoughtful is incredibly empowering.” – Breanna Kim, postbac presenter
The Spotlight Series allows postbacs to present to a broader audience with varying levels of familiarity with their specific research field. While tailoring your presentation to a specific audience is an important skill, being able to simplify your research into something more digestible can be a challenge. Yet the simplest presentations can often be the most informative and engaging. When asked to reflect on her experience as a presenter, postbac Olivia Durant noted, “Presenting to a more general audience helped me distill the purpose of my research and my results into concepts that could [be] more easily…shared with others.”
The next round of sessions in the “NIAID Postbac Research Spotlight Series” will take place this summer, and the call for speakers will open in April 2024. Sign up to speak or attend a session to support your fellow postbacs! Information will be shared on the NIAID Fellows Training SharePoint site and via email. For more information contact Jennifer West, Ph.D., NIAID Postbac/Summer Intern Program Coordinator.
Spring 2024 Postbac Speakers
January 31, 2024 | NIH Main Campus Bethesda
"Exploring the Role of Parasite MicroRNAs in Wolbachia-Host Relationships" Hailey Johnson, Systems Genomics Section, Laboratory of Parasitic Diseases (LPD)
"Microbiome-Host Responses and Predictors of Long-Term Health Outcomes in Children With Covid-19" Mickayla Bacorn, Clinical Microbiology Unit, Laboratory of Host Immunity and Microbiome (LHIM)
“Tgfbr1 LOF Mutation Augments IL-33 Mediated Proinflammatory Cytokine Release” Emily Youngblood, Food Allergy Research Section, Laboratory of Allergic Diseases (LAD)
February 14, 2024 | Twinbrook
"Prevention of Hemolysis in Erythrocytes Maintained Under P. Falciparum Culture Conditions" Alexander Burbelo, Malaria Genetics Section (LMVR)
"Sandfly Salivary Protein LJL04 Binds to ECM Proteins and Leishmania Parasite" Kristina Tang, Mosquito Immunity and Vector Competence (LMVR)
"HIV Vaccines Induce Hypofunctional CD8+ T Cells With Low Structural Avidity" Jonathan Webber, HIV-Specific Immunity Section, Laboratory of Immunoregulation (LIR)
February 28, 2024 | Rocky Mountain Laboratories
"Characterization of the ROS Response in Coxiella burnetii" Matthew Anderson, Coxiella Pathogenesis Section, Laboratory of Bacteriology (LB)
"Characterization of Disease in IFNAR-/- Mice Following Infection With Recombinant VSV Filoviruses" Olivia Durant, Immunobiology and Molecular Virology Unit, Laboratory of Virology (LV)
"Serological Screening for Crimean-Congo Hemorrhagic Fever Virus (CCHFV) in South-Central Uganda" Evan Mihalakakos, Disease Modeling and Transmission Section, Laboratory of Virology (LV)
"Optimizing the Lung Organoid Model and Differentiation of ATII into ATI" Johan Ortiz Morales, Molecular Pathogenesis Unit, Laboratory of Virology (LV)
March 13, 2024 | NIH Main Campus Bethesda
“Pre-Clinical Immunogenicity and Efficacy of an Intranasal Adenovirus type 4 (Ad4) - Vectored SARS-CoV-2 Vaccine” Breanna Kim, HIV-Specific Immunity Section, Laboratory of Immunoregulation (LIR)
“Competition Dynamics in Zika Virus Antibody-Dependent Enhancement Assays” Taylor McGee, Translational Immunobiology Unit, Laboratory of Infectious Diseases (LID)
"Deep Indel Screening Reveals Structural Constraints on Enterovirus A Evolution" Walker Orr, Quantitative Virology and Evolution Unit, Laboratory of Viral Diseases (LVD)
This document provides an overview of research and training programs opportunities for 2019-2020 available through the Division of Intramural Research.
Christine Kozak, Ph.D. is Chief of the Viral Biology Section at NIAID. The Viral Biology Section has a long-standing interest in the identification and characterization of genes that affect susceptibility to mouse leukemia viruses (MLVs) and to MLV-induced disease.
The major theme of the Laboratory of Immunoregulation (LIR) continues to be the elucidation of cellular and molecular mechanisms regulating the human immune response in health and disease. A major component of these efforts is the study of the immunopathogenic mechanisms of HIV infection and disease progression.
The rational design of strategies aimed at the prevention and treatment of HIV infection depends on delineating how HIV destroys the immune system. Our investigation of host factors involved in the evolution of HIV disease indicates that HIV pathogenesis is a multifactorial and multiphasic process. Particularly important aspects of this process that are under intense investigation include
Regulation of HIV replication by endogenous cytokines and chemokines
Regulation of expression of HIV coreceptors
HIV envelope-mediated intracellular signaling events responsible for immune dysfunction
The role of a latent, inducible reservoir of HIV-infected cells in the pathogenesis of HIV disease and its implication for antiretroviral therapy
Contribution of HIV-infected T cells, B cells, dendritic cells, monocyte/macrophages, and multipotent progenitor cells to disease pathogenesis
The role of immunomodulation in immune reconstitution during antiretroviral therapy for HIV infection
LIR researchers conduct clinical trials to determine the safety and efficacy of drugs for the treatment of HIV infection and its complication and the development of methods for immunologic reconstitution in HIV-infected individuals. Their studies of the epidemiology and pathogenesis of HIV infection and other sexually transmitted diseases are both domestic and international.
Cellular and molecular mechanisms of HIV immunopathogenesis
Regulation of the human immune system, particularly the cellular and molecular mechanisms of activation, proliferation, and differentiation of human T- and B-cells
Cellular gene expression during activation of human T and B cells
Pathogenesis and treatment of immune-mediated diseases, particularly vasculitic syndromes
Laboratory of Immunoregulation. This image may be downloaded from the NIAID Flickr site.
NIAID established the Tropical Medicine Research Centers (TMRC) program in 1991 to fund NTD research centers in disease-endemic countries. The centers are designed to conduct research on the cause, diagnosis, prevention, and treatment of NTDs, and to build in-country research capacity. The program has increased capacity of local TMRC awardees to support independent research activities, conduct future clinical trials, and implement new treatment, prevention, and vector control strategies.
Research evidence suggests that SARS-CoV and MERS-CoV originated in bats. SARS-CoV then spread from infected civets to people, while MERS-CoV spreads from infected dromedary camels to people. To date, the origin of SARS-CoV-2 which caused the COVID-19 pandemic has not been identified. The scientific evidence thus far suggests that SARS-CoV-2 likely resulted from viral evolution in nature and
The Papillomavirus: The HPV Minichromosome module is part of the Pathogens in Augmented Reality (PathogenAR) mobile app. Papillomaviruses replicate in cells of the skin, mouth and anogenital region of the human host. HPV infection can be asymptomatic, cause warts, or disrupt cell growth. On rare occasions, the cell growth becomes uncontrolled, causing cancer. About 5% of cancers worldwide are
Last Reviewed: May 9, 2024
Epstein-Barr Virus’s Molecular Mimicry Reveals a Key Site of Vulnerability
3D models showing the molecular footprints of the Epstein-Barr virus gp350 surface protein (left, in green) and the complement component Cd3 ligand (right, in pink) on the B cell surface protein complement receptor 2 (CR2; shown in duplicate side-by-side, in gray).
Credit:NIAID
Epstein-Barr virus (EBV) is a common virus that causes mononucleosis, or mono for short, and is associated with some types of cancer and autoimmune diseases. Despite EBV’s known effects and potential to cause disease, there are few therapeutic options and no licensed vaccines targeting the virus. Looking for ways to counter EBV, NIAID researchers are examining how the virus recognizes and interacts with cells at the molecular level. New research published in Immunity reveals the high-resolution crystal structure of a protein on the surface of EBV in complex with the receptor it binds to on the surface of human immune cells, called B cells. The researchers also discovered antibodies that potently neutralize EBV and found that they recognize the viral surface protein using interactions similar to those between EBV and its receptor on host cells. This research identifies a vulnerable site on EBV that could lead to the design of much-needed interventions against the virus.
EBV, also known as human herpesvirus 4, is one of the most common human viruses—nine out of ten people have or will have EBV in their lifetime. After being infected with EBV, many people experience no symptoms, but some experience symptoms of mononucleosis, such as fever, sore throat and fatigue. These symptoms are often mild but can be more severe in teens or adults. After the early stages of infection, the virus hides in the body and can emerge later in life or when the immune system is weakened. Recent studies have also found that EBV is linked to several types of cancer, autoimmune diseases including lupus, and other disorders.
A key step in EBV infection is for the virus to enter a cell in the body, which begins with the virus binding to a protein on the cell’s surface. The researchers, led by Dr. Masaru Kanekiyo, chief of the Molecular Immunoengineering Section at NIAID’s Vaccine Research Center, examined the atomic-level structure of an EBV surface protein called gp350 when bound to a protein on the surface of B cells called complement receptor type 2 (CR2). Usually, CR2 binds to a protein fragment, or ligand, called complement component C3d as a part of the immune response following a viral infection. The researchers found that the EBV protein precisely bound to the cell surface protein CR2 at the region where its natural ligand C3d binds, revealing that there is structural similarity between EBV and C3d in recognizing CR2 and how the virus exploits this interaction to enter and infect a cell.
The researchers also isolated neutralizing antibodies (nAbs)—immune proteins that neutralize EBV—from animals immunized against EBV and EBV-infected people. They found that the antibodies neutralized the virus in laboratory tests by binding to the EBV gp350 protein. They further determined the atomic-level structure of three of the nAbs when bound to EBV gp350. All three nAbs bound to gp350 at the same region of the protein—the region where it also binds to the cell protein CR2, demonstrating that this binding site is an important target on the virus for neutralization.
The way the CR2 cell surface protein binds its natural ligand C3d can be likened to a key fitting a lock. In this case, the key is a negatively charged pocket on the surface of C3d, while the lock is an arrangement of positively charged arginine residues on the surface of CR2. The researchers observed a remarkable molecular mimicry that occurred in duplicate. On one side, EBV gp350 mimics the characteristics of C3d, pretending to be the natural key that fits CR2 on the cell surface, unlocking the cell for the virus to infect it. On the other side, the anti-EBV nAbs mimic CR2, where they act as a lock to block the EBV gp350 protein from binding to a cell for the virus to infect. The mimicry existing on both sides of this lock-and-key set indicates that this interaction is an important step for EBV infection—and represents a major point of viral vulnerability, according to the researchers.
The findings define critical molecular interactions between EBV and its host cells. The researchers noted that more work is needed to apply these findings to the development of interventions, including examining whether the newly discovered nAbs can provide protection from EBV infection in animal models and people. This research may reveal new avenues to treat and prevent disease caused by this widespread pathogen.
During the transition, a notice of funding opportunity may provide links to both the FORMS-H application package and the FORMS-I application package; applicants will be responsible for choosing the appropriate form set.
Credit:NIAID
Every few years, NIH updates the application form set investigators use to apply for NIH grant awards. Such transitions provide NIH with apt moments to implement new policies and procedures.
The current form set is called FORMS-H. We will transition to FORMS-I for application due dates on or after January 25, 2025. Below, we summarize the policy changes that will accompany the switch.
Planned Policy Changes
NIH’s Simplified Review Framework for Research Project Grant Applications will replace the five standard review criteria that peer reviewers use to assess a research project grant application (Significance, Investigator, Innovation, Approach, and Environment) with three new factors: Importance of the Research, Rigor and Feasibility, and Expertise and Resources. The new framework will apply to activity codes like R01, R03, R15, R21, R61, U01, and UG3/UH3; refer to Simplified Peer Review Framework for a complete list.
NIH will also implement Revisions to the NIH Fellowship Application and Review Process to improve the likelihood that the most promising applicants are consistently identified during peer review. Specifically, peer reviewers will focus more heavily on the potential of the applicant, strength of the science, and quality of the training plan.
NIH will standardize Reference Letters to improve peer reviewers’ ability to assess the strengths, weaknesses, and potential to pursue a productive career of candidates for fellowship or career development awards. The new templates should also reduce burden on referees.
Applicants for National Research Service Award (NRSA) training program support will also notice changes with the next form set. New NRSA Data Tables are being designed to reduce administrative burden on applicants and peer reviewers. Additionally, two items—training in responsible conduct of research and the recruitment plan to enhance diversity—will begin factoring into a training grant application’s overall impact score.
Lastly, NIH will realign the information investigators must send for biographical sketches and other support, which will standardize NIH disclosure requirements with those of other federal agencies. The adjustments to preaward and progress report processes should streamline those tasks.
Lessons from Last Time
Later this year, there will be moments amid the FORMS-I transition when a notice of funding opportunity (NOFO) will provide applicants with links to both the FORMS-H application package and the FORMS-I application package. You, as the applicant, will be responsible for choosing the appropriate form set for your application.
There may be other instances in which two versions of a NOFO exist simultaneously, one using FORMS-H and the other FORMS-I. Or a NOFO may publish temporarily without any linked form set, and instead list the date when a link to the FORMS-I application package will become available. Again, in such moments, you will need to select the appropriate NOFO and form set.
When that time comes, rely on your targeted application due date to guide your selections. For a due date on or after January 25, 2025, you will need to use the FORMS-I form set. This rule of thumb holds true even if you are eligible for continuous submission or can leverage NIH’s late application policy—the targeted due date, rather than your actual submission date, is what matters.
Moreover, you will use FORMS-I for a renewal or resubmission application due on or after January 25, 2025, even if the original application used FORMS-H. In the past, NIH has allowed a grace period for administrative supplement applications (which don’t use application due dates in quite the same way); still, we encourage you to treat January 25, 2025, as a transition date for supplement requests as well.
More to Come
We will return to this topic throughout the coming year. NIH will host Webinars to further describe the policy changes listed above, several of which are already open for registration.
Genomics has become a mainstream tool, yet the amount of data produced by sequencing instruments or available on public databases presents challenges and opportunities for discovery. Bioinformatics Computational Biosciences Branch (BCBB) has expertise in many types of genomics methods applied to metagenomics, microbial genomics, transcriptomics, phylogenomics and others.
