Animal models and related services (AMRS) core

ABSTRACT Animal Models and Related Services (AMRS) Core The overall goal of Animal Models and Related Services (AMRS) Core 3 is to establish a biocontainment research support service core devoted to developing animal models of BSL3 pathogens and associated support services. Core 3 is highly relevant to the basic and translational foci of the research programs at Rutgers. No animal model perfectly reproduces the response to infection seen in humans. In Core 3, we are therefore developing different animal models that can be used to address specific aspects related to respiratory pathogen- induced disease. The newly developed animal models, and their subsequent use by RBL investigators with AMRS Core support, along with the purchase of additional specialized equipment will support and enhance the research enterprise of Rutgers investigators exploring various aspects of pathogen infection and transmission, and host disease pathogenesis. As SARS-CoV-2 transitions from a pandemic virus to an endemic one, new variants continue to appear with higher transmission rates which appear to correlate with lower pathogenicity. AIM 1 will develop animal models for investigating transmissibility of SARS-CoV-2. There have been five IAV pandemics since the 1900s, and there is ongoing concern that the current outbreak of high pathogenic H5N1 avian Influenza virus, which has affected more than 50 million birds so far, could jump to humans and cause a new pandemic. Animal models will be devloped to study IAV transmission in AIM 2. A subset of individuals has prolonged complications after COVID-19, which is known as post-acute sequalae of COVID-19 (PASC). In Aim 3, we will develop the hamster model to study PASC. The ferret respiratory tract has several similarities to humans and ferrets are highly permissive to M. tuberculosis (Mtb) and several human respiratory viruses. Therefore, we propose in Aim 4 to develop a ferret transmission model and test its suitability for investigating transmissibility of clinical strains of Mtb and in identifying the genes that Mtb requires to survive the successive stresses associated with transmission. More than half of the people with microbiologically cured tuberculosis (TB) exhibit some form of pulmonary impairment after TB (PIAT) affecting long-term respiratory health. In Aim 5, we will develop a pre-clinical mouse model of pulmonary impairment after TB (PIAT) for evaluating adjunct host directed therapeutics. Establishment of animal models to test efficacy of newly discovered compounds with anti- TB activity in vitro would significantly advance the TB drug program. In Aim 6, we will stablish a pre-clinical murine model for efficacy testing of new TB drug candidates. As each of these six aims are completed, the AMRS Core's technical staff will then aid RBL investigators in the performance of these animal models in their own grant supported research. The personnel, instrumentation and experience acquired achieving these aims will also be harnessed to develop and support additional animal models as required to address new biothreats, pandemics or emerging infectious diseases.