HIVE Center Collaborative Development Program: Request for Applications

Background

The HIV Interaction in Viral Evolution (HIVE) Center is a multi-institute research consortium led by Bruce Torbett at The Scripps Research Institute La Jolla, CA and Stefan Sarafianos at the University of Missouri. The HIVE Center integrates the efforts of 14 research groups representing leaders in the field of HIV structural biology.  Our goal is high-resolution characterization of the structural and dynamic relationships among interacting macromolecules that shape the HIV life cycle.

The HIVE Center’s core goal is a comprehensive structural and dynamic depiction of the major HIV enzymes (protease, reverse transcriptase, and integrase) and structural proteins (matrix, capsid, and nucleocapsid) as well as interactions with their cellular partners during viral replication, assembly, maturation, and integration. As existing drug targets, the HIV proteins provide a rich base of structural, biological, and evolutionary data that will serve to inform our far-reaching goals. We also propose to explore drug resistance and the resulting evolution of HIV as a platform upon which to characterize the dynamic relationships among interacting viral-host macromolecular complexes. Our approach encompasses diverse disciplines and methodologies including computational, crystallography, electron microscopy, mass spectrometry, hydrogen-deuterium exchange, eukaryotic cell-based protein expression, synthetic chemistry, and virology.  It is geared toward gaining new structural, biochemical and biophysical insights into the interdependence of viral-host mechanisms and the potential for using this information for the discovery of new chemical entities that modulate the viral life cycle and will be potentially useful for therapeutic intervention.

Some of the specific features of the HIV life cycle that remain incompletely characterized from a structural vantage point that we wish to address are: 1) structures of the HIV Gag, Gag-Pol, and Pol polyprotein precursors; 2) structures of the HIV transcription initiation complex with HIV RT, host tRNA, and viral RNA; 3) structures of macromolecular complexes that involve cellular host factors and are relevant to HIV biology; 4) conformational dynamics of HIV proteins and their complexes probed by small-molecule allosteric effectors and inhibitors.

Application

The HIVE center is currently seeking collaborators to join us in working to characterize and understand the structural and dynamic viral-host interactions of HIV polyprotein precursors and their mature enzyme counterparts during the HIV life cycle.

Interested applicants are required to contact a HIVE Center member to sponsor their application, ideally before beginning the application process—not all projects are suitable since some may duplicate existing HIVE efforts.  Prospective applicants are encouraged to visit the list of currently active members of the center and their areas of research, contact information, and other information relevant to the HIVE center.

A brief summary of the proposed work and how it will contribute to the HIVE Center’s research objectives must be included in the HIVE Center face page submitted with their application (see application details below).  Investigators at an early stage in their career and/or new to HIV research are strongly encouraged to apply.  We will accept proposals for review from eligible applicants that contribute complementary methods.  Some examples include but are not limited to:    

• Imaging of cellular complexes relevant to HIV biology by cryo-electron tomography, correlative light and electron microscopy (CLEM), SANS, solid-state NMR, or other techniques
• Single molecule assays for exploring the structural dynamics of cellular complexes and processes relevant to HIV biology
• Single cell approaches to study aspects of HIV biology through genomics, transcriptomics, epigenetic, proteomics, and metabolomics analyses
• High-throughput ex vivo and computational modeling approaches to study HIV drug resistance and evolution

Funding: Grants of approximately $60,000-$100,000 (direct costs) will be awarded to 2 or 3 investigators for one year.

The deadline for submission of proposals is midnight (EST), October 2, 2017. Successful applicants will be notified by the end of October. Funding will begin on November 1, 2017.

Proposals should be submitted electronically as PDF files to Eddy Arnold at eddyarnoldlab@gmail.com and a plan of collaboration with the sponsoring HIVE Center investigator must be included.

Eligibility: Faculty at the level of Assistant Professor or higher who are eligible for NIH funding. Women, minorities, veterans, and disabled persons are encouraged to apply.

Format: Single-spaced, ½-inch margins, Arial typeface, font size 12

Required Components (in indicated order):

HIVE Center face page that includes a statement of collaboration and sponsoring HIVE Center member.

Detailed Budget and Budget Justification

NIH Biosketch (4 page maximum)

Proposal Text (sections 1 - 4, 4 pages total)

1. Specific Aim(s)
2. Background
3. Preliminary Data
4. Research Design and Methods
5. Timeline and Specific Milestone(s) (Not to exceed 1 page)
6. References Cited

Questions: Questions about the application and review processes should be directed to eddyarnoldlab@gmail.com.

Funded Individuals:

Funded investigators will be required to follow all NIH regulations/requirements, including those related to animal use, human subjects, recombinant DNA, biohazards, select agents, and reporting.  In addition, participation in HIVE Center activities, including monthly teleconferences, meetings, and annual symposia, is required.