Summary/Abstract The Broad’s GCID will make breakthrough progress by testing key hypotheses and filling fundamental knowledge gaps about the mechanisms responsible for infectious diseases. We will do this by generating and analyzing ‘omic data from a variety of key pathogens and characterizing key interactions between pathogens and their hosts. To drive this mission, we have created a Technology Core that brings an unmatched combination of cutting-edge capabilities for the study of pathogens — including viruses, bacteria, fungi, parasites and their vectors — and their hosts. The Technology Core will generate a variety of high throughput data, from a wide range of sample types, utilizing our state-of- the-art genomics facility. To do this, we will draw upon our expertise operating, managing and optimizing robust, large- and small-scale data generation processes, and on our extensive and sophisticated sample handling and tracking capabilities. We will improve existing methods to increase their utility in our studies, for example by reducing to practice new enabling methodologies, enabling increased scale and efficiency, improving data quality and decreasing costs. We will enhance our approaches to pathogen hybrid selection and long read sequencing, and also implement new protocols for low input RNA- and metagenomic-sequencing. Finally, building on our long track record of innovation in genomics, we will create new technologies and establish new capabilities that were not previously practical or possible to open new fundamentally avenues for our Research Projects. These include systematic methods to study gene function, to enrich pathogen nucleic acids from those of the host, and to sequence from single cells, as well as methods for simultaneous capture of genomes and plasmids from single cells and ribosome profiling proteomics. Importantly, the technical expertise of the Technology Core is closely integrated with the mechanisms of oversight and management of the Administrative Core. Collectively our GCID will apply these methods to understand mechanisms of virulence, transmission and drug resistance, to define the critical interactions between pathogens and their hosts and microbial communities to improve our prevention, diagnosis and treatment of infectious diseases.