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Research Focus

The living cell is home to thousands of molecular machines that perform an astounding array of functions. Our group uses cryo-electron microscopy to characterize the structures of these large protein complexes in order to better understand their role in the cellular environment. In determining the molecular architecture of these nanomachines, which are generally made up of one or more copies of a single or even dozens of proteins, we gain a more comprehensive understanding of the mechanisms that underlie biological processes.

Our current research focuses on the manner in which unwanted intracellular proteins are recognized and degraded by the 26S proteasome. Although the overall subunit organization of the proteasome has been determined, there are many questions surrounding the manner in which substrates are recognized by or transported to the proteasome, as well as how targeted proteins are unfolded and translocated to the proteolytic chamber. The answers to these questions would significantly improve our understanding of proteasome’s role in cellular homeostatis, potentially revealing novel approaches to detect and suppress the onset of tumorigenesis and neurodegeneration.

Education

B.S., Biochemistry, Binghamton University, 2002
Ph.D., Biophysics, The Scripps Research Institute, 2009

Selected References

Lander GC*, Estrin E*, Matyskiela ME*, Bashore C, Nogales E, Martin A. Complete subunit architecture of the proteasome regulatory particle. Nature 482, 186-91 (2012) *co-authors

Wiedenheft B*, Lander GC*, Zhou K, Jore MM, Brouns SJ, van der Oost J, Doudna JA, Nogales E. Structures of the RNA-guided surveillance complex from a bacterial immune system. Nature 477, 486-9 (2011) *co-authors

Lander GC, Stagg SM, Voss NR, Cheng A, Fellmann D, Pulokas J, Yoshioka C, Irving C, Mulder A, Lau PW, Lyumkis D, Potter CS, Carragher B. Appion: an integrated, database-driven pipeline to facilitate EM image processing. J Struct Biol 166, 95-102 (2009)

Lander GC, Tang L, Casjens SR, Gilcrease EB, Prevelige P, Poliakov A, Potter CS, Carragher B, Johnson JE. The structure of an infectious P22 virion shows the signal for headful DNA packaging. Science 312, 1791-5 (2006)