Collaborative Development Program

2021 Request for Applications

Background

The HIV Interaction and Viral Evolution (HIVE) Center is a multi-institute research consortium led by Bruce Torbett (University of Washington) and Stefan Sarafianos (Emory University). The HIVE Center integrates the efforts of 18 research groups representing leaders in the field of HIV virology, with emphasis in structural, computational, and biophysical approaches. Our goal is high-resolution characterization of the structural and dynamic relationships among interacting macromolecules in the HIV life cycle.

The HIVE Center’s core goal is a comprehensive structural depiction of the major HIV enzymes (protease, reverse transcriptase, and integrase) and structural proteins (matrix, capsid, and nucleocapsid) interactions with their viral and host 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 resistance and evolution in HIV as a platform upon which to characterize the dynamic relationships among interacting macromolecular structures.  Our approach encompasses diverse disciplines and methodologies including computation, cryo-EM, crystallography, hydrogen-deuterium exchange, NMR, synthetic chemistry, fluorescence microscopy, 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 are 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) molecular structures of HIV integrase, capsid complexes, as well as the HIV transcription initiation complex with HIV RT, host tRNA, viral RNA, HIV proviral DNA / chromatin configuration; 3) conformational dynamics of HIV proteins and host cell factors as well as HIV-host cell complexes probed by small-molecule allosteric effectors and inhibitors.

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 proteins and host factors that affect viral function. We will accept proposals for review from eligible applicants that contribute complementary methods.  Some examples include, but are not limited to:

  • Cryo-electron tomography of HIV core or GUV-related complexes.
  • Chromosome conformation capture methods applied to HIV and chromatin organization.
  • Structural or virological aspects of host factors relevant to HIV biology.

The Application

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 HIVE center website (http://www.hivecenter.net/team/) for an updated list of currently active members of the center and their areas of research, contact information as well as 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.

Funding: Grants of approximately $140,000 (total costs) will be awarded to 2 investigators for one year.

The deadline for submission of proposals is midnight (EST), August 2, 2021. Successful applicants will be notified by the end of the day August 24. Funding will begin on October 1, 2021.

Proposals should be submitted electronically as PDF files to­­­­­­­­­­­­­­­­­­ betorbet@uw.edu and  karen.kirby@emory.edu

A plan of collaboration with the sponsoring HIVE Center investigator must be included.

Eligibility: Faculty eligible for NIH funding may apply. Women, minorities, veterans, and disabled persons are strongly encouraged to apply.

Required Components (in indicated order):

HIVE Center CDP Grant Application Face Page and Forms 2021 The forms include the face and budget pages, collaboration and sponsoring HIVE Center member information, and instructions. These must be included in the application.