Cell Biology and Biophysics Unit - Division of Intramural Research
Antonina Roll-Mecak, Ph.D., Investigator
Dr. Roll-Mecak received her undergraduate degree in chemical engineering from The Cooper Union for the Advancement of Science and Art in 1996. She pursued her graduate training in Stephen Burley's laboratory and received her Ph.D. in molecular biophysics from the Rockefeller University in 2002. Her structural and biochemical studies on translation GTPases helped elucidate the mechanism of assembly of translationally competent ribosomes. She conducted her postdoctoral training with Ron Vale at the University of California, San Francisco where she investigated the mechanism of macromolecular machines that regulate the microtubule cytoskeleton. Dr. Roll-Mecak joined NINDS and NHLBI as an investigator in 2010. Dr. Roll-Mecak received for her work a Searle Scholar Award, a Burroughs Wellcome Career Award in Biomedical Sciences, a L'Oreal for Women in Science Fellowship Award, a Pathway to Independence Award (K99), a Damon Runyon Cancer Research Postdoctoral Fellowship, a Hillblom Foundation Fellowship and was awarded the Henry W. Reddick Fund Prize and Medal for Mathematics. Her lab combines biophysical and cell biological approaches to understand the mechanism underlying intracellular organization and movement, with a focus on the microtubule cytoskeleton.
In addition to providing structural support, microtubules form a complex and dynamic intracellular "highway" that delivers molecular cargo from one end of the cell to another -which in the case of neuronal cells can span several feet. Given the continually changing cell physiology, this delivery system undergoes constant remodeling as cargo is transported to different destinations with high temporal and spatial accuracy. Failures in this highly coordinated transport system lead to disease and mutations in genes that encode microtubule dynamics regulators have been implicated in neurodegeneration, cardiovascular disease, cancers and viral infections.
Not surprisingly, tubulin, the building block of the microtubule network is one of the most post-translationally modified proteins in the cell. My laboratory combines biophysical and cell biological approaches to understand the interplay between microtubules and their regulators and how the chemical complexity of microtubules tunes the behavior of motors and microtubule associated proteins. Despite the abundance and complexity of tubulin modifications, their effects on microtubule behavior are still poorly understood. Is the microtubule more than just a structural strut, or a naive roadway for cellular components to transit along? Is there a "tubulin code", written in the rich language of the post-translational modifications of tubulin that, much like a histone code, provides specificity and regulation to cellular dynamics and to the trafficking of motor proteins and their cargo on the cellular highway? How functional diversity is imparted to different microtubules is a central question in cell biology with important implications for human health.
Selected Recent Publications
Garnham, C. P. and Roll-Mecak, A
The chemical complexity of cellular microtubules: Tubulin post-translational modification enzymes and their roles in tuning microtubule functions, Cytoskeleton, 2012, vol. 69(7), pp. 442-463.
Szyk, A., Deaconescu, A.M., Piszczek, G., Roll-Mecak, A
Tubulin tyrosine structure reveals adaptation of an ancient fold to bind and modify tubulin, Nature Struct. & Molec. Biol, 2011, vol. 8(11), pp. 1250-8.
Roll-Mecak, A. and McNally, F.J.
Microtubule severing enzymes, Curr. Opin. Cell Biol, 2010, vol. 22(1), pp. 96-103.
Roll-Mecak, A. and Vale, R.D.
Structural basis for microtubule severing by the hereditary spastic paraplegia protein spastin., Nature, 2008, vol. 451(7176), pp. 363-7.
Roll-Mecak, A. and Vale, R. D.
The Drosophila Homologue of the Hereditary Spastic Paraplegia Protein, Spastin, Severs and Disassembles Microtubules., Curr. Biol., 2005, vol. 5(7), pp. 650-55.
Roll-Mecak, A., Cao, C., Dever, T.E., and Burley, S.K.
X-ray structures of the Universal Translation Initiation Factor IF2/eIF5B: Conformational Changes on GDP and GTP Binding., Cell, 2000, vol. 103, pp. 781-792.