Research: Biophysics and structural biology.
361 Frick Chemistry Lab
The basis for movement and force generation in muscle and non-muscle cells is the actin-based microfilament system. Actin is a 43 kilo-dalton protein that has been highly conserved since the dawn of the eukaryotes over a billion years ago. Primordial precursor forms of actin and tubulin exist in bacteria, pointing to an even earlier origin for polymerizing proteins as generators of movement. Its emergence at the same time as the eukaryotic cell membrane, replacing the rigid cell walls of prokaryotes, enabled cells to exhibit a wide variety of dynamic shape variation at the cell edge. These movements are the structural basis for cell migration, tension generation, engulfment of other organisms, muscle contraction, and various modes of nutrient transport. Perhaps the most dynamic manifestation of the versatility of the actin microfilament system is the human nervous system, where cycles of polymerization and depolymerization of actin are an essential element of neural plasticity.
Schutt's laboratory has used x-ray crystallography, selected-site mutagenesis, and other biophysical techniques to reveal the structures and roles of actin-binding proteins. This large family of proteins, including profilin, gelsolin, actin depolymerization protein, tropomyosin, and myosin, controls the dynamic organization of the actin microfilament system. Recently, Schutt has become interested in the structural biology of human neuro-developmental disorders, such as autism, where genomic variation in genes for key actin-binding proteins are well-correlated with dysfunctional synaptic connections. The architectonic challenge of bridging human behavior to molecular changes in the human brain must involve a full realization of the potential of the actin microfilament system to continuously reorganize into functional structures at cell edge and inwards towards the cell nucleus.
- Grenklo, S., Hillberg, L., Rathge, L.S.Z, Pinaev, G., Schutt, C.E., Lindberg, U. “Tropomyosin Assembly Intermediates in the Control of Microfilament System Turnover”. Eur. Cell Biol. 87:905-920 (2008.
- Lovelace, J.J., Murphy, C.R., Daniels, L., Narayan, K., Schutt, C.E., Lindberg, U., Svensson, C., Borgstahl, G.E.O. "Protein Crystals can be Incommensurately Modulated", J. Appl. Cryst. 41:600-605 (2008).
- Lindberg U., Karlsson, R., Lassing, I., Schutt, C.E., Hoglund, A-S, "The Microfilament System and Malignancy", Seminars in Cancer Biology, 18:2-11 (2008).