The Scripps Research Institute has made a major commitment to the acquisition, development and expanded use of advanced technologies for the post-genome era of modern biomedical research.
Scripps Florida's Translational Research Institute combines basic research with advanced technology platforms or cores to develop potential lead compounds that can prevent, treat or cure disease. Those platforms include the Cell Based Screening Core, Genomics Core, and Proteomics Core. These core technology groups work closely with the various academic departments as well as the drug discovery group within the Translational Research Institute to bring advanced technologies to bear on complex biological problems.
Researchers in the Cell-Based Screening Core utilize high-throughput technologies to develop a systematic description of gene function encoded by the human genome, and a more comprehensive understanding of the genetic basis for human disease. They provide Scripps Research scientists, as well as select outside collaborators, access to genome wide collections of cloned or complementary DNA and silencing RNA that can be used to investigate cellular models of signal pathways and biochemical phenotypes.
The Genomics Core handles data collection and initial data processing related to microarray analysis. Microarrays, also known as gene chips, are basically glass or silicon wafers with short fragments of RNA and/or DNA deposited on their surface. By placing cell or tissue samples on these wafers, scientists can study which genes are being expressed, the levels of expression and how that expression changes over time.
The Proteomics Core focuses on the application of liquid chromatography and mass spectrometry to identify, quantify, and characterize proteins and post-translational protein modifications. Research scientists in this division are involved in scientific collaborations with numerous Scripps Florida scientists as well as several outside investigators at other state and national research institutions.
The Flow Cytometry Core allows scientists to measure and analyze the characteristics of single particles, normally cells, as they move in a stream and are passed through a laser. Thousands of cells can be analyzed by a flow cytometer in a single second, while at the same time separating and isolating specific cells. Among the measurements derived from flow cytometry are the size, relative fluorescence and complexity of the particle.
The Nuclear Magnetic Resonance Core uses the magnetic properties of certain nuclei to allow scientists to study molecular structure. A wide variety of information can be gathered using NMR including protein and nuclei acid structure and function. At present, Scripps Florida has two nuclear magnetic resonance instruments. The two machines run 24 hours a day, 365 days of the year; one is connected to the Internet so that scientists can quickly access data from their offices and laboratories.
The objective of the Drug Discovery group is to translate basic research into potential therapeutics by integrating the work of the biomedical faculty, who provide therapeutic area expertise and in-depth knowledge of target biology, with the advanced technology group who help enable target validation, assay development and biological models.
The Drug Discovery group includes the following components: Discovery Biology, Drug Metabolism and Pharmacokinetics (DMPK), TRI-Informatics, Lead Identification and HTS, and Medicinal Chemistry. These groups collaborate in the discovery and development of therapeutic agents for unmet medical needs for a variety of diseases.
The Discovery Biology Division is responsible for selecting and characterizing molecular targets thought to be involved in human diseases. Once a target is selected, Scripps Florida scientists use biochemical, molecular, and cellular techniques to understand its mechanism of action and evaluate how well the compound performs as a potential therapy and how effectively and safely it interacts with its intended target.
The Drug Metabolism and Pharmacokinetics (DMPK) group supports the development of new drugs through physical measurements and formulation, in vitro and in vivo metabolism, and pharmacokinetics. These tools can tell scientists how stable a drug candidate is, how rapidly a potential drug is cleared from the body, how a potential drug interacts with enzymes in the intestines and liver, and how well a drug candidate crosses the blood-brain barrier.
The TRI-Informatics group manages and mines the wealth of scientific data—both existing data generated from projects like the Human Genome Project and all the new data generated by Scripps Research scientists. Informatics investigators work with other groups to design software interfaces and platforms that can assist in experiments such as the development of special applications to analyze data streams from high throughput technology and analytical tools for large-scale proteomic studies.
The Lead Identification and HTS group is involved in high throughput screening of large compound collections against biological targets involved in various diseases. Promising candidates from these screens are then examined further in collaboration with scientists in the DMPK, Discovery Biology, Informatics, and Medicinal Chemistry groups. Narrowing the research field to those few compounds that show promise for development is one of the most crucial jobs in the development of novel drug candidates.
The High Throughput Screening (HTS) Core operates within the Lead Identification Division. Its technologies are available to external investigators through a variety of scientific collaborations.The Medicinal Chemistry group designs and modifies biologically active chemical entities that target specific enzymes or receptors with the goal of optimizing their therapeutic properties and value. Working in concert with their colleagues in Lead ID, Discovery Biology, and DMPK, investigators in Medicinal Chemistry are focused on a variety of disease areas, including cancer, arthritis, and Parkinson's disease.