Abstract

The recent pandemic of COVID-19 due to infection with the SARS-CoV-2 coronavirus has created an urgent need to understand the biological mechanisms of pathogenesis of this new disease. The SARS-CoV-2 is a coronavirus with a slightly less than 30 kilobases (kb) long RNA genome that encodes 26 proteins that interact with several hundred human proteins and initiate a number of pathogenic steps. Here we use the genetic model Drosophila melanogaster to understand gene and protein function involved in COVID-19. We will generate a library of UAS-cDNA constructs and transgenic flies to express and functionally assess the viral proteins. We will also generate transgenic flies for over 300 genes in the human genome involved in viral replication and COVID-19 disease. We will generate Drosophila reagents for the Drosophila homologs of these human genes using a unique drop-in technology and we will update the online hub for the dissemination of these resources to Drosophila labs throughout the world.

Public Health Relevance

The COVID-19 pandemic disease is caused by a new coronavirus named SARS-CoV-2 which has 26 protein coding genes. In this project, researchers will study each of these genes by expressing them in fruit flies and assessing the consequences of their expression. They will create the tools to study over 300 human genes that have been shown to bind to the viral proteins and hence may be involved in COVID-19.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
3R24OD022005-05S1
Application #
10167394
Study Section
Program Officer
Zou, Sige
Project Start
2016-06-01
Project End
2024-05-31
Budget Start
2020-08-01
Budget End
2021-05-31
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Genetics
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Ansar, Muhammad; Chung, Hyung-Lok; Taylor, Rachel L et al. (2018) Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts. Am J Hum Genet 103:568-578
?entürk, Mümine; Bellen, Hugo J (2018) Genetic strategies to tackle neurological diseases in fruit flies. Curr Opin Neurobiol 50:24-32
Marcogliese, Paul C; Shashi, Vandana; Spillmann, Rebecca C et al. (2018) IRF2BPL Is Associated with Neurological Phenotypes. Am J Hum Genet 103:245-260
Tan, Kai Li; Haelterman, Nele A; Kwartler, Callie S et al. (2018) Ari-1 Regulates Myonuclear Organization Together with Parkin and Is Associated with Aortic Aneurysms. Dev Cell 45:226-244.e8
Liu, Ning; Schoch, Kelly; Luo, Xi et al. (2018) Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder. Hum Mol Genet 27:2454-2465
Chao, Hsiao-Tuan; Liu, Lucy; Bellen, Hugo J (2017) Building dialogues between clinical and biomedical research through cross-species collaborations. Semin Cell Dev Biol 70:49-57
Wang, Julia; Al-Ouran, Rami; Hu, Yanhui et al. (2017) MARRVEL: Integration of Human and Model Organism Genetic Resources to Facilitate Functional Annotation of the Human Genome. Am J Hum Genet 100:843-853
Chao, Hsiao-Tuan; Davids, Mariska; Burke, Elizabeth et al. (2017) A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3. Am J Hum Genet 100:128-137
Wangler, Michael F; Yamamoto, Shinya; Chao, Hsiao-Tuan et al. (2017) Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research. Genetics 207:9-27
Luo, Xi; Rosenfeld, Jill A; Yamamoto, Shinya et al. (2017) Clinically severe CACNA1A alleles affect synaptic function and neurodegeneration differentially. PLoS Genet 13:e1006905

Showing the most recent 10 out of 11 publications