Colin Echeverría Aitken
At a molecular level, life requires the interpretation of the information stored in genes to synthesize the functional molecules for which each gene is a recipe. I study the molecular machinery that reads genes to assemble protein molecules. Because proteins are largely responsible for performing the myriad molecular tasks of life, this translation process is essential to life, enabling cells to grow, develop, and respond to external stimuli. Not surprisingly, translation is highly regulated in healthy cells. This regulation is disrupted during viral infection, cancer, neurodegenerative diseases, and many other maladies. Our lab studies how the ribosome — an ancient molecular machine responsible for assembling proteins in all forms of life — is assembled on a gene and prepared to synthesize protein. This initiation event is one of the most important readings of the genetic code and is the focus of most cellular regulation of translation. We interrogate translation initiation at the molecular level by purifying the individual molecular components involved in this pathway, enabling us to reconstitute translation initiation within a test tube and investigate it using biochemical and biophysical tools. To complement this approach, we make use of next-generation sequencing technologies that permit us to follow the position of individual ribosomes on every gene being translated in living cells.
Yourik, P., Aitken, C.E., Zhou, F., Gupta, N., Hinnebusch, A.G., Lorsch, J.R. (2017) “Yeast eIF4A enhances recruitment of mRNA regardless of their structural complexity.” eLife. 10.7554/eLife.31476
Jinsheng, D., Aitken, C.E., Lorsch, J.R., and Hinnebusch. A.G., and (2016) “Rps3/uS3 residues in the 40S ribosomal entry channel stabilize preinitiation complex assembly at initiation codons in vivo.” PNAS. 114(11)E2126-E2135.
Aitken, C.E., Beznosková, P., Vlčkova, V., Chiu, W.L., Zhou, F., Valášek, L., Hinnebusch. A.G., and Lorsch, J.R. (2016) “Distinct roles for eIF3 at the pre-initiation complex entry and exit channels.” eLife. 10.7554/eLife.20934
Llácer, J.L.*, Hussain, T.*, Marler, L., Aitken, C.E., Thakur, A., Lorsch, J.R., Hinnebusch, A.G., and Ramakrishnan, V. (2015) “Conformational differences between open and closed states of the eukaryotic translation initiation complex.” Molecular Cell. 3(2):497-508.
Aitken, C.E., and Lorsch, J.R. (2012) “A Mechanistic Overview of Eukaryotic Translation Initiation.” Nature Structural and Molecular Biology. 19(6):568-76.
Aitken, C.E., and Puglisi, J.D. (2010) “Following the intersubunit conformation of the ribosome during translation in real time.” Nature Structural and Molecular Biology. 17: 793-800.
Uemura, S., Aitken, C.E., Korlach, J., Flusberg, B.A., Turner, S.W., and Puglisi, J.D. (2010) “Real-time tRNA transit on single translating ribosomes at codon resolution.” Nature. 464(7291): 1012-7.
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