Current Research: Molecular/Cellular
Understanding how a disease state differs from a healthy system is critical for identifying potential treatments and preventative measures for neurological diseases. PNR&D investigators share a broad array of molecular and cellular biology expertise to enable exploration using state-of-the-art techniques. By combining research at all levels, from genes and proteins through the individual cells, mixed cell systems, rodent models, and on to clinical patient investigation, a complete picture of disease and treatment can be obtained.
Molecular Biology
Motor neurons overexpressing genes. In addition to the gene under examination, a gene that codes for "green fluorescent protein" is included to quickly identify neurons that are genetically altered.
PNR&D researchers examine the genetic material, the DNA, in health and disease to discover mutations or differences that may lead to neurodegenerative disorders. The functions of specific genes can be determined by deletion or over-expression of those genes in an experimental system. Techniques such as DNA/RNA arrays allow researchers to screen hundreds of genes in a single experiment, thereby identifying families of genes that are altered in neurological disease.
Protein Biology/Biochemistry
Proteins are responsible for cellular structures, and the majority of biological activities. PNR&D investigators study how healthy and diseased neurons differ in the expression and cellular locations of important proteins. Expression, activation, and localization changes can be tracked by labeling proteins with antibodies and visualizing them by a variety of techniques, such as gel electrophoresis (using electrical charge to sieve proteins through a porous substance), fluorescent microscopy, or electron microscopy. PNR&D investigators use chemical agents that alter protein function or expression in neurons to understand intracellular disease pathways and to target points of therapeutic intervention.
Cell Culture
By isolating the specific cells that are affected in a particular disease, the pathways that control the life and death of that cell can be explored. PNR&D investigators are experts in the isolation and culture of many types of cells that are affected in neurodegenerative diseases. These cells can then be used to simulate the disease in a Petri dish. Cells isolated from metastatic or non-metastatic brain cancer are used for the neuroblastoma research. ALS is investigated at the cellular level by isolating and culturing rodent motor neurons. Similarly, diabetic neuropathy is studied at the cellular level using cultures of rodent sensory neurons taken from the dorsal root ganglion, and also using the neuronal support cells of the nerve, known as Schwann cells. The Schwann cells are essential for nerve regeneration following an injury. Neuronal injury can also be studied in these cell models. Living neurons can be observed in real-time (AVI video format) to assess the ability to grow and regenerate the nerves.
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Animal Models
Experimental disease states that mimic the human conditions are essential tools for exploration of the disease process and the effects of therapeutics. These models are produced in many ways. For example, transferring the mutant gene that produces some human cases of ALS into a mouse produced the same inherited disease in the mice. Some types of diabetes arose spontaneously in mice and have proved useful models for human disease, while acute diabetes is produced by removing the insulin-secreting cells in the mouse or rat. Experimental drugs and gene therapies are introduced to these animal models, and animals are assessed for physiological, biological and chemical changes in the disease process.
