Biological Sciences

Mission

The missions of the Biological Sciences Group group are to: develop instrumentation, consumables and other tools to accelerate drug discovery research in small animal models; and to develop novel therapeutic and diagnostic approaches for cancer, neurological disease and biowarfare agent exposure. The biological sciences group also provides support within PSI in a broad range of areas including antimicrobial development, biochemical and biological fuel cell development, immunoassay development for diagnostic and sensor applications, and tissue engineering

Core Competencies

Core competencies include molecular and cellular biology, small animal model development, drug discovery and diagnostics assay design, and nucleic acid based therapeutic and diagnostic technologies. The Biological Sciences Group personnel skills include microbiology, biochemistry, cell and molecular biology, and biochemical and whole organism assay design

Recent Activities Using Small Animal Models

PSI is developing tools to automate research, drug discovery and toxicology assays using zebrafish embryos and larvae. PSI has developed the SideView^tm microplate, a 96-well plate that features rectangular wells that align samples with right angle prisms. This novel microplate enables collection of clear images of the sides of zebrafish larvae, and other organisms, in microwells using an inverted microscope. This technology along with companion technologies that enhance the use of the microwells is expected to accelerate vertebrate developmental biology research; and aid in drug discovery and toxicology testing. These microplates have been developed into a commercial product that is available at (SideView Microplate). As part of those efforts, PSI has developed algorithms to identify fluorescently labeled blood vessels in zebrafish and assess their integrity. These efforts have been supported both internally and through the NIH.

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(a) bottom view and (b) side view images of zebrafish larvae that express green fluorescent protein in blood vessel walls

A second, novel tool has been developed to accelerate discovery of new pharmaceuticals that affect cardiac output and also provides a moderate-throughput, early stage cardiac toxicology platform. That device uses Fourier Domain-Optical Doppler Tomography to generate 2-D and 3-D structural videos and extract blood velocity information. The atrium and ventricle are clearly visualized in structural videos thus enabling identification of heart rhythm defects. Blood velocity and cross-sectional area are measured at the aorta to provide robust cardiac output measurements.

Brightfield (top) and fluorescence (bottom) images of a C. elegans nematode that expresses a green fluorescent protein (AcGFP) in neuronal nuclei

Other Recent and Ongoing Activities

PSI has developed a cell culture model (osteoblast model) for bone production in which cellular proteins are labeled using fluorescent proteins. Up to three fluorescently tagged proteins in a single cell can be visualized using a confocal imaging system equipped with solid-state laser sources.

Osteosarcoma cells that express an HcRed-β-actin fusion protein

Current Research Thrusts Include:

• Novel System for Automation of Zebrafish Lipid Assays:

- Sponsor: NIH/NIDDK

- Objective: Develop tools for a full automation of a zebrafish lipid assay.

- Products: SideView^tm microplate and accessories.


• Automated Screening System for Modifiers of Cardiac Output in Zebrafish

- Sponsor: NIH/NHLBI

- Objectives: Develop a fully automated device that measures cardiac output in zebrafish for discovery of new pharmaceuticals and for assay of cardiac toxicity.


• Single-Step Aptamer Selection Procedure

- Sponsor: Air Force

- Objectives: Develop method for rapid aptamer selection against emerging threat agents.


• Development of Contrast Agents for NIR Diagnostic for Ovarian Cancer

- Sponsor: NIH/ NCI

- Objectives: Develop diagnostic tool to detect ovarian cancers.



Area Leadership

Dr. Anthony Ferrante

Since receiving his Ph.D. in 1992, Dr. Anthony Ferrante has developed a broad scientific background that spans bacterial physiology and molecular genetics, mammalian virology (HIV), and small animal model, biochemical assay development and instrumentation development. Since joining PSI in 2003, Dr. Ferrante has focused on development of imaging technologies for biomedical and bioresearch applications. Dr. Ferrante was the Principal Investigator on a confocal imaging program funded by NASA and on four programs (three active) to develop high-speed imaging technologies for use with zebrafish larvae and other small animal models. The technology developed during one of those programs is currently entering commercialization. Dr. Ferrante currently serves as the Biological Sciences Group Leader.

Anthony A. Ferrante Physical Sciences Inc. 20 New England Business Center Andover, MA 01810-1077 Telephone: (978) 689-0003 Fax: (978) 689-3232 ferrante@psicorp.com

 

Biological Sciences