Dr. Ulrich H.E. Hansmann, Erik Alred
Describe your undergraduate research or creative project:
Alzheimer’s Disease is characterized by the formation of Amyloid beta (A beta) fibril plaques in the brain. Solid state NMR (ssNMR) allows one to resolve the structure of these fibrils but, instead of a single structure, leads to an ensemble of configurations that are compatible with the NMR signals. Typically, only the lowest energy conformer is considered in computer simulations that probe the stability of fibrils and their binding with drug candidates. However, this practice may produce data that are not physiologically relevant if the NMR entries differ significantly in stability or binding affinities. For this reason, we have investigated the stability differences in the NMR ensembles of a patient-derived fibril model and two in-vitro models that allow also the comparison of different staggering patterns. We observe significant variations in molecular flexibility, compactness, and secondary structure which suggest that the complete NMR ensemble must be considered for a physiologically relevant description of Abeta fibrils.
Explain what you learned or give advice to fellow students:
As a postdoc once described to me, there are few experiences as satisfying or as rewarding as discovering that one thing that essentially no one else knows. The sense of accomplishment from producing research that no one else has ever ventured to do alone is worth the difficulty and tedium involved in research. My recommendation is that more people, especially undergraduates, partake in this same experience. Regardless of major, type of research, or field, I recommend everyone be involved in research.
Awards and/or presentations:
Poster Presentation Oklahoma Supercomputing Conference 2015, "Differences in Amyloid Fibril Models of Alzheimer's Disease" given at University of Oklahoma Stephenson Technology Center. Work Supported by NID-NIDDK STEP-UP program, Penn State Coordinators, Oklahoma Center for Advancement of Science and Technology grant #HR14-129, National Science Foundation grant #CHE-1266256, OSCER Boomer compute time.
Poster and Oral Presentation NIH-NIDDK STEP-UP Symposium 2015, "Differences in Amyloid Fibril Models of Alzheimer's Disease" given at NIH-NIDDK Nascher Center. Work Supported by NID-NIDDK STEP-UP program, Penn State Coordinators, Oklahoma Center for Advancement of Science and Technology grant #HR14-129, National Science Foundation grant #CHE-1266256, OSCER Boomer compute time.
Phillips, M. (2016, April). Differences in Amyloid Fibril Models of Alzheimer's Disease. Poster session presented at the University of Oklahoma's Undergraduate Research Day, Norman, OK.
"On the lack of polymorphism in Aβ‐peptide aggregates derived from patient brains." Protein Science 24, no. 6 (2015): 923-935.