# Core 2

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $265,257

## Abstract

THE HARC CENTER: HIV ACCESSORY AND REGULATORY COMPLEXES
GENETICS CORE
SUMMARY
To support all HARC Center Projects, the Genetics Core will provide innovative high-throughput methods for
the discovery and functional characterization of HIV-host protein complexes in primary cells (i.e. activated
primary CD4+ T cells, resting primary CD4+ T cells, and primary macrophages). Working in tandem with the
Proteomics, Structural Biology, and Computational Cores, we will develop the HARC endogenous protein
structure (HEPS) platform for the discovery and functional characterization of different HIV-host protein
complexes by inserting affinity tags at genomic loci to allow affinity purification of endogenous protein complexes
directly from HIV infected primary cells. Using our breakthrough CRISPR knock-out (CRISPRko), activation
(CRISPRa), interference (CRISPRi), and knock-in (CRISPRki) technologies in primary human T cells, we will (1)
generate a systematic map of proviral and antiviral HIV-interacting host factors, (2) functionally validate novel
HIV-host interactions, (3) undertake endogenous deep mutational scanning of specific protein domains to identify
critical host-pathogen interaction interfaces, and (4) introduce/replace small stretches of DNA at targeted
genomic sites to study the function of specific genetic variants. Collectively, these genetic studies will strengthen
the central HARC mission to understand interactions between HIV accessory proteins and host factors and open
new experimental and therapeutic avenues for a broader HIV research community. In summary, the Genetics
Core will develop a toolbox for genetic perturbations to complement innovative structural biology and proteomic
efforts.

## Key facts

- **NIH application ID:** 10829950
- **Project number:** 5U54AI170792-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** JENNIFER A DOUDNA
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $265,257
- **Award type:** 5
- **Project period:** 2022-07-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829950

## Citation

> US National Institutes of Health, RePORTER application 10829950, Core 2 (5U54AI170792-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10829950. Licensed CC0.

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