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Indiana University Bloomington

Faculty from several departments participate in our Graduate Program. They are listed according to the following research area.

students in labs

Jared CochranJared Cochran

Assistant Professor, Molecular and Cellular Biochemistry Department

Office: Simon Hall 405C

Phone: 812/855-6935

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Education

B.S. (2000) University of Pittsburgh - Biological Sciences
Ph.D. (2005) University of Pittsburgh - Biochemistry and Enzymology
Postdoctoral Fellowship (2011) Dartmouth College - Structural Biology and Biophysical Chemistry

Research

One of the main objectives of the research performed in the Cochran laboratory is to study and understand the details of mechanochemical force transduction in kinesin superfamily motor proteins and elucidate how microtubules stimulate their ATPase activity. Conventional kinesins utilize the chemical energy stored in ATP in order to produce directed force along microtubule filaments. The details of force generation vary greatly among kinesins: the motility of different kinesin subfamilies can be towards either end of the polar microtubule, some subfamilies are processive motors - taking multiple steps along a filament without dissociating, and others are non-processive - requiring multiple heads working in concert in order to achieve motility. Additionally, a growing number of non-motile kinesins have a very different cellular function - the regulation of microtubule dynamics. Coupled to these divergent cellular activities are differences in kinetic ATPase cycles, as well as structural changes in the conserved motor core. These projects seek to investigate the details of kinesin structure and function in order to understand how subtle differences (e.g. amino acid substitutions and variation of loop lengths) affects the kinetic cycles and force generating characteristics of unconventional kinesin family motors.

To achieve this goal, we will study the detailed structure and thermodynamic energy landscape of an unconventional kinesin, kinesin-10/NOD to determine differences between motile and non-motile kinesin mechanochemistry. In addition, we will characterize our engineered biochemical "metal switch" for kinesin and myosin ATPases as well as small G proteins using a novel experimental approach to probe functional metal-enzyme interactions. Finally, we will investigate the high resolution structure of a kinesin motor in complex with tubulin in order to visualize the detailed mechanism by which interaction with microtubules accelerates the kinesin ATP hydrolysis cycle. The knowledge acquired from the proposed research will expand our understanding of kinesin-MT and other protein-MT systems and will provide valuable insights into possible avenues for therapeutic targeting to combat diseases such as Alzheimer's, Parkinson's, and cancer.

Representative Publications

Cochran JC, Thompson M, and Kull FJ (2013) “Metal Switch Controlled Myosin II from Dictyostelium discoideum Supports Closure of Switch 1 During ATP Binding is Coupled to Myosin Detachment from Actin Filaments” J Biol Chem In Review

Cochran JC and Kull FJ (2013) "A Molecular Motor Finds Its Track" Nat Struct Mol Biol "News and Views" In Press

Audu CO, Cochran JC, Pellegrini M, and Mierke DF (2013) “Recombinant production of TEV cleavable human parathyroid hormone” J Pep Sci 19: 504-510

Waitzman JS, Larson AG, Cochran JC, Naber N, Cooke R, Kull FJ, Pate E, and Rice SE (2011) “The loop 5 element structurally and kinetically coordinates dimers of the human kinesin-5, Eg5” Biophys J 101: 2760-2769

Cochran JC, Zhao YC, Wilcox DE, and Kull FJ (2011) “A Metal Switch for Controlling the Activity of Molecular Motor Proteins” Nat Struct Mol Biol 19: 122-127

Zhao YC, Kull FJ, and Cochran JC (2010) “Modulation of the Kinesin ATPase Cycle by Neck Linker Docking and Microtubule Binding” J Biol Chem 285: 25213-25220

Cochran JC, Sindelar CV, Mulko NK, Collins KA, Kong SE, Hawley RS, and Kull FJ (2009) “ATPase cycle of the nonmotile kinesin NOD allows microtubule end tracking and drives chromosome movement” Cell 136: 110-122

Cochran JC and Kull FJ (2008) “Kinesin motors: no strain, no gain” Cell 134: 918-919

Cochran JC, Krzysiak TC, and Gilbert SP (2006) “Pathway of ATP hydrolysis by monomeric kinesin Eg5”  Biochemistry 45: 12334-12344

Cochran JC and Gilbert SP (2005) “ATPase mechanism of Eg5 in the absence of microtubules: Insight into microtubule activation and allosteric inhibition by monastrol” Biochemistry 44: 16633-16648

Cochran JC, Gatial JE III, Kapoor TM, and Gilbert SP (2005) “Monastrol inhibition of the mitotic kinesin Eg5” J Biol Chem 280: 12658-12667

Cochran JC, Sontag CA, Maliga Z, Kapoor TM, Correia JJ, and Gilbert SP (2004) “Mechanistic analysis of the mitotic kinesin Eg5” J Biol Chem 279: 38861-38870

Skiniotis G, Cochran JC, Muller J, Mandelkow E, Gilbert SP, and Hoenger A (2004) “Modulation of kinesin binding by the C-termini of tubulin” EMBO J 23: 989-999

Coughlan CM, Walker JL, Cochran JC, Wittrup KD, and Brodsky JL (2004) “Degradation of mutated bovine pancreatic trypsin inhibitor in the yeast vacuole suggest post-endoplasmic reticulum protein quality control” J Biol Chem 279: 15289-15297