Current Research: Computational Methods
The 3-dimensional shape of a protein dictates the types of motions that are accessible to the structure. These motions are what allow the protein to carry out its biological function. A more complete understanding of this structure–function relationship is critical. There are numerous data collection methods that help elucidate this connection, but they provide an incomplete picture. The use of computational methods can escape these limitations.
Experimental finding are used to guide the formulation of models, which are then used to guide experimental exploration. Computational models are currently employed in the search for disease mechanisms.
Bioinformatics is a broad field of research combining computer science and biology to help accelerate the research process. PNR&D researchers are collecting massive quantities of data, all of which could be potentially relevant to neurological disease. There is also a large body of data made freely available to the public that may contain useful information. The bioinformatics effort at PNR&D aims to bring all of this data together, and get a fast, reliable and detailed picture of what all of this data can tell us. Our bioinformatics work is done in collaboration with the National Center for Integrative Biomedical Informatics (NCIBI).
Recent bioinformatics projects include:
- Analysis of the effect of drug treatment on neuropathy in diabetic mice. 15,000 genes were measured for being on or off in normal mice, mice with diabetes and diabetic mice that received treatment. By looking at how the genes are turned on and off, we learned more about how diabetes causes nerve damage and also how at least one drug prevents that process from happening. These results will help us develop safer and more effective treatments for nerve damage caused by diabetes.
- Analysis of the portion of the nerve in the leg compared to the portion near the spine. Because diabetes damages the parts of the nerve farthest from the spine first, we compared how genes are turned on and off in the leg (the sciatic nerve) compared to the part close to the spine (the dorsal root ganglion). These different parts of the nerve are showing very different properties, and we continue to examine the potential meanings behind the gene regulation we observe.
- Science progresses at an incredible pace, and more scientific papers are published every day than any single scientist could read. We developed a program that can scan all of the papers published and available on-line (currently numbering in the millions) for the names of genes. It can then tell you what genes are most important to a particular subject. Our investigators can use this tool to discover new connections between diseases and gain better insight into what is know (and unknown!) about how neurological diseases work.
- We examined six recent studies of oxidative stress in the nerve, looking for common trends in genes that are turned on or off in all of them. This super-analysis lets us get a higher degree of certainty that our results are reliable, and helps cut down on time spent investigating leads that might not be reproducible. Especially when combined with the paper searching software described above, this analysis has given PNR&D investigators an unparalleled level of insight into what the root causes of neurological disease are and how they might be corrected.
