Collaborative Development Award 

Request for Applications

This RFA describes a Collaborative Development Program that will fund four researchers who will enhance our efforts and benefit from interactions with the CHEETAH Center. We particularly encourage applications from faculty members at the Assistant Professor level, as well as from researchers from groups who are traditionally underrepresented in science.

The CHEETAH Center for the Structural Biology of HIV Infection, Restriction and Viral Dynamics

To initiate an infection, HIV-1 must complete a series of transformations that include fusing with the target cell membrane, releasing the viral core particle into the cytoplasm where it begins to reverse transcribe the viral RNA into DNA and moves into the nucleus, losing the external capsid (termed “uncoating”), and integrating the viral DNA genome into the host chromosome. These early steps in HIV-1 replication can be challenging to study because infections are initiated by single virions, and because many of the key transformations occur deep within the cell. Our Center has a focus on uncovering the molecular mechanisms that underlie these key processes in the first half of the viral life cycle.

Although HIV-1 ultimately gains the upper hand in untreated infections, human cells are not defenseless victims, but rather can sense and inhibit HIV-1 infections using a series of powerful innate immune responses. Nearly every step in the first half of the HIV-1 life cycle has a corresponding innate immune sensing or restriction activity, and defining these processes in molecular detail is another focus of our studies. Our Center will gain great synergy from the interplay between our studies of viral processes and their counteracting restriction mechanisms.

Complex biological processes like HIV/AIDS can only be truly be understood by considering all possible resolution scales, from the molecular, through the cellular, to the organismal level. Studies in another focus area for our Center are designed to create and apply approaches for studying and modulating viral dynamics, latency, and rebound across resolution scales, and to leverage advances in molecular virology and protein design to create new broad-acting antiviral systems and virus-inspired delivery systems. In essence, our goal is to create the foundations necessary to tackle new frontiers in HIV-1 biology and medicine, including the development of cure strategies, broad antiviral therapeutics, and methods for delivering biologic therapeutics efficiently into specific cell types.

In summary, the fundamental missions of our CHEETAH Center for the Structural Biology of HIV Infection, Restriction and Viral Dynamics are: 1) to define the molecular mechanisms that allow HIV-1 to infect cells, 2) to characterize the innate immune defenses that help protect cells against HIV-1 infection, 3) to perform multiscale analyses of viral latency and rebound and learn how to modulate viral dynamics, and 4) to develop and apply new technologies that will advance our capabilities for studying HIV-1 biology.

Our overall goals are to continue to develop HIV into an unparalleled model system for studying how a human virus interacts with its host, and to lay the groundwork for the development of new antiviral therapies.

Strategies and Objectives

Our primary goal is to recruit and support talented researchers working on important emerging areas of virus-host interactions in the general areas of HIV Infection, Restriction and Viral Dynamics who will interact successfully with CHEETAH Center personnel, benefit from access to Center resources, and help us to achieve Center objectives. We also intend to: 1) Open important new problems and targets to the range of approaches supported by our Center, 2) Attract talented new investigators into the HIV field, 3) Enhance opportunities for synergy by broadening our interactions with the HIV research community, and 4) Introduce important new technologies into our Center. No single investigator can fulfill all of these qualities, but our portfolio of awards will collectively promote these objectives. We anticipate that successful applicants will range from researchers who are identifying and validating new HIV host factors and wish to pursue structural studies (as broadly defined), to researchers with expertise in emerging technologies that can be applied to advance ongoing Center projects. Center Investigators, and scientific capabilities are provided on our website: http://cheetah.biochem.utah.edu, and prospective applicants are strongly encouraged to contact Center investigators to discuss their projects and develop plans for collaboration.

Expectations

Funded investigators will be required to: 1) follow NIH guidelines and regulations, including those related to animal use, human subjects, and recombinant DNA, 2) participate fully in CHEETAH Center activities, including biweekly video conferences and annual meetings, and 3) provide annual progress reports.

Questions

Questions regarding application logistics should be directed to the CHEETAH Center Manager, Dr. John McCullough (mccull@biochem.utah.edu). Questions regarding scientific collaborations or application strategies should be directed to the CHEETAH Center Director, Dr. Wes Sundquist (wes@biochem.utah.edu), or to individual CHEETAH Center Investigators (see http://cheetah.biochem.utah.edu).

Application Process

Eligibility Four awards will be given to independent, grant-eligible researchers at universities and research institutes that qualify for NIH support. International applicants are also eligible, subject to NIH approval.

The initial cycle of four collaborative development grant applications will be due on April 3rd, 2023, and funding will begin on May 1st, 2023. Grants will initially be for one year, with renewal for a second year possible with satisfactory progress. CDA awards will be for total costs of $102,000 in year 1 and a total

of $115,500 in Year 2. Qualified applicants should submit their proposal (see below) directly by email to Dr. John McCullough, CHEETAH Center Manager: mccull@biochem.utah.edu

Application Format

Applications should be submitted as a single pdf file comprising the following materials: 1) Completed NIH PHS 398 face page, including signature from authorized institutional official (downloadable from http://grants.nih.gov/grants/funding/phs398/phs398.html) 2) NIH Biosketch, see https://grants.nih.gov/grants/forms/biosketch.htm for instructions

3) Research Proposal with the following sections (4 pages maximum including figures, but excluding References Cited). A) Specific Aims B) Research Strategy a. Significance b. Innovation c. Approach C) References Cited 4) Collaborative Proposal describing how your project will benefit from and contribute to CHEETAH Center objectives (1 page) 5) Itemized Budget and Justification including travel expenses to both the NIH Structural biology Related HIV/AIDS and CHEETAH annual meetings (up to 4 pages) Applications should follow NIH R01 application guidelines for font, character size, format, etc.