Biocontainment Laboratory—Boston University National Emerging Infectious Diseases Laboratory

• To perform innovative research on the pathogens that cause emerging infectious diseases, including the interactions between the pathogen and the host, and to understand disease pathogenesis. 
• To develop and test advanced diagnostic tools, therapeutics and vaccines against these pathogens for the public’s health. 
• To train scientists, both established investigators as well as the next generation, in the safe and secure study of emerging pathogens, and to support a national response in the event of a biodefense emergency. 

• Investigators in academia, not-for-profit organizations, industry, and government studying biodefense and emerging infectious diseases may request the use of the facility through collaboration with faculty and staff or by contract. 

• Please contact the NEIDL directly for further information (neidl@bu.edu).

Laboratory and Analytical Support

• Veterinary services. The veterinary staff consist of a lead veterinarian and technical staff that provide the necessary expertise for support of disease modeling for development of treatments in the ABSL-3 and ABSL-4 environment. A range of models are available with appropriate and redundant support infrastructure that connect with the services discussed below. 
• Pathology services. The NEIDL has a Comparative Pathology Laboratory which offers standard and advanced histotechnology imaging services. The service is equipped to carry out routine and advanced microscopic interpretation of tissues, including histomorphological interpretation, multiplexed fluorescent immunohistochemistry, multiplexed in situ hybridization (ISH), and quantitative image analysis utilizing the commercial software Halo^TM by Indica labs.
• Clinical Chemistry Services. The NEIDL has parallel setups for blood analysis in different containment spaces (ABSL-4 and ABSL-2). Each dedicated laboratory space has a Vetscan HM5 hematology machine, two Vetscan VS2 chemistry analyzers, and two VSpro coagulation analyzers.
• Immunology services. This provides training on user friendly instrumentation, including flow cytometer analyzers at BSL-4 (11 color BD LSRFortessa) and BSL-2 (11 color LSR II), Biorad Bioplex 200 analyzers for cytokine analysis (in BSL-4 and BSL-2), automated ELISPOT readers (CTL, at BSL-4 and BSL-2) which allows for automated viral plaque counting as well as ELISPOT. Cell purification can be carried out using Miltenyi GentleMacs (BSL-4) and AutoMACS Pro cell separation (BSL-3). Various plate readers are available for immunology and other analyses (Tecan Spark M20 multimode,Tecan M200 and M1000), ELISA readers, etc. LUNA-II automated cell counters and Invitrogen Countess ICommentsI automated cell counters are available.
• Virology Services (VS). The Virology Services (VS) unit provides four services to the research community. These include 1) incoming BSL-4 virus strain receipt, propagation, and storage, 2) validating inactivation protocols for these viruses, and providing inactivated material to the research community, 3) tool development or implementation of innovative technologies to drive the BSL-4 field forward (in collaboration with other service units within the BSL-4), and 4) performing BSL-4 cell culture experiments for researchers who do not have access to BSL-4 facilities.

cGLP or cGMP Capabilities

cGLP capabilities are in place and are used for all work with NHPs. A laboratory is fitted for receipt of biologics, and archive space for documents and pathology blocks are established. 

• Equipment and space monitoring. In addition to the Building Automation system, critical equipment and spaces are additionally monitored using the GxP compliant ELPRO Technologies system. Temperature, humidity, differential pressure, carbon dioxide, oxygen, light, and door openings can be monitored. NEIDL has deployed this system selectively to monitor incubators (CO2, temperature, and humidity), rooms (temperature and humidity), refrigerators and freezers (temperature) that are associated with Well Documented studies. The system has been implemented to record the parameters in perpetuity and to alert key stakeholders if there are excursions from pre-set ranges.
• Telemetry. The DSI PhysioTel large animal telemetry system and PhysioTel L and M series digital implants are used to monitor large animals. Parameters include continuous core body temperature and activity, systemic blood pressure, left ventricular pressure, ECG, heart rate, respiratory rate and volume and can be expanded to include EEG or other pressures or biopotential measurements. The DSI PhysiTel system allows for minimal hands-on interactions by technical staff by offering the researcher remote capabilities to start and stop data collection and for simultaneous remote data analysis. DSI Anipill is used for monitoring temperature of small animals. 

Specialized Areas

• High-throughput Screening (HTS) Services. This has been operationalized to include automated visual screening of virus infected cells treated with small molecule inhibitors, and can be adapted to any virus or cell target. The HTS services unit provides high capacity evaluation of small molecules, antibodies and siRNA for inhibition of virus infection. The unit has a strongly pharmacological driven approach to identify high potency inhibitors using high-density 384 well plates through scalable, semi-automated but BSL-4 compatible processing of materials and capacity in the 1000’s of compounds per week. Robotic plate mapping, plate replication, virus dispensing, plate image capture and automated image analysis provide high reproducibility over short time frames.
• Imaging services include a Zeiss 200M with conventional and oil immersion (100x, 63x) lenses and climate-controlled stage and time lapse, mosaic and optical sectioning capacities, a Nikon Ti2-E microscope (equipped with high quality objectives including 100x oil immersion lambda NA 1.45 lens and a Photometrics sCMOS camera), and Biotek Cytation high throughput imaging system with an automated plate loader and Autoquant software. EVOS M500 fluorescent cell imagers are available at every biosafety level, as are other standard compound and inverted microscopes. For pathology services a Nikon Eclipse 50i bright field microscope and a Nikon Eclipse epi-fluorescent microscope are available. The latter is equipped with an LED light source and DAPI/FITC/TRITC/&Cy5 filter sets. In addition there is an Akoya Mantra 2.0 multispectral microscope that allows for imaging high plex images with up to 9 concurrent biomarkers at the region of interest level. A Mizar lightsheet microscopy system is being installed in the BSL-4 for live cell imaging. It includes diode-based laser spanning 405, 488, 561 and 638 nm) and equipped with a Scientific CMOS camera.
• Whole animal imaging. For imaging there is a Perkin Elmer IVIS Spectrum instrument for bioluminescence imaging of rodents.
• Insectaries. The NEIDL includes spaces for the integration of insectaries into the containment laboratories. There is a functioning insectary for mosquito transmission studies at ACL-2 and ACL-3. The insectary has 4 dedicated rooms that permit the isolation of infection studies (with insectary incubator, BSC and screen room for working with infected mosquitoes) from the areas designed for rearing mosquitoes (with 2 insectary incubators), and integrates with the necessary animal facilities. A 3 room suite for vector transmission studies using ticks or other insect vectors can be activated in the future in the BSL-4 footprint.
• Aerobiology. The NEIDL has 2 dedicated aerobiology suites, one each at BSL-3 and at BSL-4 which allows aerosol delivery of pathgens or therapeutics to animals from mice to non-human primates. These include a class III biosafety cabinet/glovebox, which integrates with the animal transfer spaces. These include the interlocking HEPA-filtered airflow transfer carts that are battery operated. The suites are supported by automated AeroMP aerosol system (Biaera Technologies). 
• Single cell sequencing. Single-cell omics technologies, including the 10X Chromium, Seqwell, and FluentBio Inc’s PIPseq single-cell approaches that allow the creation of single-cell emulsions from which sequencing libraries can then be created are available. 10X Chromium controllers are present at every biosafety level for studies of virus-host interactions. 

Animal Capabilities

ABSL-3 and ABSL-4 facilities can be used for a variety of species. Each holding room has a dedicated procedure space. 

Animal species include murine (mouse, hamster), guinea pig, ferret, and non human primates. Other species can be accomodated for studies. 

Animal Models 

Animal inoculation capability/routes of challenge include IN (intranasal), IM (intramuscular), IT (intratracheal), IP (intraperitoneal), IV (intravenous), SC (subcutaneous), ID (intradermal), IC (intracerebral), IO (intraocular), scarification, and various mucosal routes using a mucosal atomization device, and by aerosol. 

Animal models can be developed for most pathogens using appropriate inoculation routes. 

Pathogens

NEIDL faculty have the expertise to work with a variety of pathogens as every biocontainment level. Pathogens that are currently in house include various filoviruses, flaviviruses, alphaviruses, buyaviruses, paramyxovirues, arenaviruses, and coronaviruses. Various bacterial pathogens include Mycobacterium tuberculosis, Franscisella tularensis, and Yersenia Pestis. 
 

The National Emerging Infectious Diseases Laboratories (NEIDL) is housed on the Boston University Medical Campus within close proximity to the School of Medicine, School of Dental Medicine and School of Public Health and their associated research facilities, and Boston Medical Center, the principal teaching hospital for the medical school. The Medical Campus also houses the following: 

• Core facilities (http://www.bumc.bu.edu/busm/research/cores/) 
• Animal Science Center which includes animal facilities for BSL-2 and BSL-1 animal work
• Center for Regenerative Medicine
• Center for Network Systems Biology
• Clinical and Translational Science Center

The Boston University Medical Campus is a short shuttle bus ride from the Boston University Campus on the Charles River. The BU campus includes the following specialized research areas: 

• School of Engineering and its Biomedical Engineering Department 
• Biologic Design (“synthetic biology”) Center
• The Hariri Institute for Computing and Computational Science
• Photonics Center
• Center for Molecular Discovery