# Identification and Characterization of Norovirus Cofactors for Entry

> **NIH NIH R00** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $249,000

## Abstract

Project Summary/Abstract
 This proposal describes a four year career development plan and a research strategy for Dr. Robert
Orchard to transition from a postdoctoral fellow to an independent academic faculty position investigating host-
pathogen interactions. The mentored phase of the award (K99) will be completed under the continued
guidance of Dr. Herbert `Skip' Virgin in the Department of Pathology and Immunology at Washington University
School of Medicine. The overall research goal of the proposal is to determine molecular mechanisms of
norovirus cofactors upon viral entry.
 Candidate: I have a long standing interest in understanding the molecular mechanisms underlying
complex host-pathogen interactions. I graduated summa cum laude from Texas A&M University with a degree
in Microbiology. I subsequently joined the Molecular Microbiology Graduate Program at University of Texas
Southwestern Medical School. For my doctoral thesis in Dr. Neal Alto's laboratory, I described how bacterial
virulence proteins usurp the host cytoskeletal machinery and engineer pathogenic-signaling circuits within the
complex environment of the cytoplasm of eukaryotic host cells. I then began a postdoctoral fellowship under
the mentorship of Dr. Skip Virgin. During my fellowship in Dr. Virgin's lab, it has been my goal to couple my
experiences with dissecting host-pathogen signaling networks with his ability to define the in vivo relevance of
host-pathogen interactions in animal models. To this end, my research project has been focused on
understanding the molecular mechanisms of murine norovirus (MNoV) replication and tropism due to its robust
in vitro and in vivo systems. Specifically, we recently completed a whole-genome CRISPR screen for host
genes required for MNoV replication. We discovered that MNoV binds a proteinaceous receptor, CD300lf, that
is necessary both in vitro and in vivo for MNoV replication and when expressed in human cells sufficient to
break the species barrier of MNoV replication. Additionally, our work described a novel, unidentified cofactor in
serum required for efficient MNoV binding to cells. This work is the foundation for the research proposal
outlined here. I plan to focus the remainder of my fellowship on obtaining professional skills and scientific
insight necessary to transition to a tenure-track position.
 Career Development Plan: During my final year as a postdoctoral fellow, I will focus a significant
amount of effort (15%) to developing the professional skills challenging to me that are necessary for successful
independent investigators. I have assembled a career advisory committee composed of Dr. Daved Fremont,
Dr. Michael Diamond, and Dr. Thaddeus Stappenbeck that will evaluate my progress in overcoming
deficiencies in scientific writing and data presentation, mentoring, and laboratory management along with my
scientific progress. Additionally, I will attend specific seminars both within and outside of Washington
University to en...

## Key facts

- **NIH application ID:** 9980887
- **Project number:** 5R00DK116666-04
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Robert C. Orchard
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-08-03 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980887

## Citation

> US National Institutes of Health, RePORTER application 9980887, Identification and Characterization of Norovirus Cofactors for Entry (5R00DK116666-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9980887. Licensed CC0.

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