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Principal Investigator: KENNETH E PALMER
Organization: UNIVERSITY OF LOUISVILLE
Fiscal Year: 2021
Award: $3,333,333
Funding agency: National Institute of Allergy and Infectious Diseases
The University of Louisville Regional Biocontainment Laboratory (RBL) is an operational unit of the University’s
Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases (CPM). The CPM operates
the only Biosafety Level 3 laboratories and animal research facilities available to researchers in the
Commonwealth of Kentucky. As such we are a regional resource for two Carnegie Research I (highly research
intensive) Universities—the University of Louisville and the University of Kentucky—as well as for the local
biotechnology industry and other universities and non-profit organizations. The University of Louisville has been
an outstanding steward of the RBL, paying meticulous attention to the facility needs. However, after a decade,
we have encountered some challenges, primarily with obsolescence of control systems, and wear and tear on
some of the building air handling systems. The necessary HVAC upgrades are already being addressed by the
University, but we request support from NIAID through this G20 for additional facility related upgrades and
modernization of research equipment
SPECIFIC AIMS
We propose to address specific facility operational needs in both the fixed building infrastructure and in upgrading
and modernizing our in vivo and in vitro research capabilities. We propose incorporating modern state-of-the-art
instrumentation to build solid foundations for innovations in biodefense and emerging infectious disease
research. The building systems upgrades that directly affect operations of the containment space will be
scheduled during the annual preventative maintenance shutdown periods to be conducted in
November/December 2021 and 2022. Similarly, new in vivo and in vitro research equipment shall be installed
during the annual shutdown to allow for service professionals to install and commission the equipment without
needing to address biosafety training and Select Agent-specific standard operating procedures.
Aim 1: Repair, renovate and modernize RBL building systems to enhance functions and operations of
the existing research facilities. We propose to address specific facility operational needs in the fixed building
infrastructure. We shall upgrade critical facility systems that are facing imminent obsolescence and rectify one
major facility design defect that placed some inconveniences and limitations on research operations: the BSL-3-
ABSL-3 passthrough boxes. The long-term commitment of the CPM is to support basic and translational
research that leads to the development of countermeasures for biodefense and emerging infectious agents.
These upgrades will secure our ability to maintain our BSL-3 research program and continue to develop
innovative countermeasures against biodefense and emerging infectious disease threats.
Aim 2: Enhance and modernize the CPM RBL in vivo research capabilities. The COVID-19 pandemic
validated the significance and need for ABSL-3 facilities such as we have at the CPM. Over the past 14 months
our in vivo research facilities were heavily utilized to support development of novel COVID-19 therapeutics,
vaccines and other prophylactic strategies. Until COVID-19 the vast majority of our in vivo research utilized
murine models, with sporadic use of ferrets for influenza studies. Recently, we have made extensive use of the
Golden Syrian Hamster (GSH) model. Consequently, we have a practical need to expand our caging for medium
sized rodent models. Moreover, emerging data on post-COVID human pathologies impacting different organ
systems—lung, cardiovascular, neural and renal in particular—raise the need for more sophisticated tools for
assessing physiological function in research models. To this end, we propose to elevate our in vivo research
facilities by adding Promethion metabolic isocaging systems that record animal metabolic and behavioral data
and allow us to integrate research studies with our existing gnotobiotic rodent core. We shall also add telemetry
capabilities to precisely record body temperature, heart rate and blood pressure metrics. For lung function
assessments, we will add rodent plethysmography capabilities. These research infrastructure enhancements will
build new collaborations with our colleagues in centers of excellence in environmental health, cardiovascular
disease, diabetes and obesity. We will also consolidate existing collaborations with our Functional Microbiomics,
Inflammation and Pathogenicity COBRE by facilitating use of gnotobiotic animals to assess the impact of
microbiome communities in pathogenesis of emerging infectious diseases. In vivo imaging capability is an
extremely useful adjunct to physiological and most-mortem pathology assessments. Our existing IVIS optical
imaging system is nearing obsolescence, and needs upgrading to secure ongoing research studies, particularly
in Yersinia pestis and Burkholderia pseudomallei infection models.
Aim 3: Enhance and modernize the CPM RBL in vitro research capabilities. The CPM RBL is a wellequipped facility, but the vast majority of the research instrumentation was installed as the University cost-share
contribution to the RBL construction between 2007 and 2010. We have a meticulous equipment maintenance
and service program coordinated by Marlene Steffen and funded by the Executive Vice President for Research
annual budget to the CPM, which has kept all of our equipment fit for purpose. Over the past decade, technology
Contact PD/PI: PALMER, KENNETH E
Program Narrative Page 7
for analysis of immune cell function by flow cytometry has become significantly more sophisticated. We propose
to enhance and modernize our flow cytometry analytical capabilities by adding a Becton Dickinson
FACSymphony analyzer with 4 laser/16 color capabilities and high throughput system that will accommodate
96/384-well plates. This will significantly expand the speed, throughput and sophistication of the data acquisition,
complementing our existing 11-year-old FACSAria II cell sorter. We have existing high throughput screening
capabilities in our High Throughput Biology Core. Most of the HTPB equipment is also a decade old. We propose
that our biodefense and emerging infectious disease research programs would benefit immensely by acquisition
of the Cytation C10 high throughput confocal microscopy instrument that allows rapid collection of high quality
and high-resolution quantitative data under normal cell and tissue incubation conditions. Several of our faculty
have critical need for this instrument to be located in our RBL BSL-3 laboratories to facilitate their research on
emerging viruses and bacterial pathogens.
Terms: <Area><Chills><Collection><Communicable Diseases><Confocal Microscopy><Data><Disease Outbreaks><Emerging Communicable Diseases><Emerging Infectious Diseases><Ensure><Equipment><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Goals><Hydrogen Oxide><Illumination><Image><In Vitro><Infectious Disease Pathway><Infectious Diseases><Infectious Diseases / Laboratory><Infectious Diseases Research><Infectious Disorder><Investigators><Kentucky><Laboratories><Laboratory Animal Production and Facilities><Laboratory Research><Lighting><Link><Medicine><Metabolic><Modernization><NIAID><National Institute of Allergy and Infectious Disease><Normal Cell><Normal Tissue><Normal tissue morphology><Outbreaks><Physiologic><Physiological><Plethysmography><Process><Research><Research Animal Facility><Research Infrastructure><Research Personnel><Research Subjects><Researchers><Resolution><Seasons><Secure><System><Telemetries><Telemetry><Therapeutic><Treatment Efficacy><Universities><Water><bio-threat><biodefense><biothreat><data acquisition><data complexity><discover vaccines><flow cytophotometry><imaging><improved><in vivo><infectious disease model><instrument><instrumentation><intervention efficacy><mouse model><murine model><operation><prevent><preventing><repair><repaired><research facility><response><therapeutic efficacy><therapy efficacy><vaccine discovery>