About the TMC-GCID

The unifying objective of the Texas Medical Center Genomics Center for Infectious Diseases (TMC-GCID) is to combine the latest advances in sequencing technology and computational analysis with next-generation human organotypic culture systems to address major knowledge gaps in host–pathogen–microbiome interactions at mucosal epithelial surfaces. Our focus on both microbes and human responses will provide an unparalleled and comprehensive approach to understanding two critical elements that dictate disease. By fulfilling this objective, we will not only identify new pathogenic and host drivers of disease but will also define novel preventive, therapeutic, and diagnostic targets for some of the most impactful human pathogens.

The unifying theme of the Research Projects within the TMC-GCID is that infectious diseases represent the sum of dynamic interactions and adaptive changes involving both pathogens and host responses – the collision of two very different worlds that interact at mucosal epithelial surfaces of human tissues. All pathogens that we propose to study acutely infect or chronically colonize the epithelium. A comprehensive approach that integrates pathogen, host, and microbiome components is essential to unravel this complex biological web and gain mechanistic insights. Using our collective expertise and technological capabilities, three overarching knowledge gaps will guide the TMC-GCID as we address each knowledge gap in our overall aims (Fig.1).

The TMC-GCID Research Projects and Cores

Project 1 – Bacteria: will build on discoveries made from dissecting genomic elements of pathogenic members of the Enterobacteriaceae that associate with human intestinal mucosa colonization and translocation.

Project 2 – Virus: will continue integrated analyses of human norovirus and respiratory syncytial virus full-length genomic sequences and characterization of the ecological niche of samples from clinically relevant patient sub-groups for new understanding of viral replication, recombination and evolution, induction of disease and host factors required for susceptibility to infection and pathogenesis.

Project 3 – Fungi: will examine the impact of commensal Candida albicans on gut health and susceptibility to disease. Mapping the fungal-host-microbiome interplay in relevant gut niches using the latest genomic, metagenomic and metatranscriptomic technologies will greatly improve the understanding of how commensal fungi can influence gut homeostasis.

Project 4 – Cryptosporidium: Several discoveries were made in phase one of this TMC-GCID. Including, how Cryptosporidium interacts with the human intestinal microbiome to determine infection outcomes, assembly of a highly accurate and complete reference genome for C. parvum isolate and examining the kinetics of infection across different GIT segments in differentiated HIOs from various donors.

All research projects will continue to utilize human intestinal and lung organoid cultures along with niche-specific, defined microbial communities supplied by the Organoid and Minibioreactor Array Cultivation Core. Meanwhile cutting edge, high-throughput sequencing strategies and technologies and the latest analysis tools and outputs will be supplied, and disseminated, by the Sequencing Analysis and Resource Dissemination Core.

The TMC-GCID is supported by the National Institute of Allergy and Infectious Diseases of the National Institute of Health under the award number 1U19AI144297-01.

TMC-GCID Administrative Core Team