Genetically encodable MRI contrast agents, electrically activated yeast and optogentics.
2005-2009
Research during my undergraduate (2005-2009, MIT Biological Engineering) studies focused on protein engineering using directed evolution and rational design. During my freshman and sophomore years at MIT, I worked in the Langer and Jasanoff Labs on development of fMRI contrast agents. We performed mutagenesis and high throughput testing of ferritin and P450-BM3 in order to use them as MRI contrast agents responsive to changes in molecular signaling, activation of protein kinase A (PKA) (1), and release of dopamine (2),. During the summer of 2007, I joined the Arnold Lab at Caltech as a visiting student, where I mutated the P450-BM3 for improved thermal stability, performed directed evolution screens, and designed a method for statistical analysis of binding curves that allowed us to obtain the highest affinity dopamine binder among our protein mutants (2). Subsequently, I joined the Boyden Lab (Synthetic Neurobiology group at MIT Media lab) for the remainder of my time at MIT, where I worked on engineering GPCRs to become responsive to light. We obtained a number of domain-shuffled receptors, one of which showed light-induced changes in cAMP levels. During the summer after college, I joined a group of talented students at the Polytechnic University of Valencia (Spain), and proposed an idea to use electrical impulses to trigger bioluminescence in yeast. Resulting project was entered in iGEM, a worldwide synthetic biology competition, and won 3rd place worldwide (3) and a few other awards.
Image: Bacterial clones cultured during my undergraduate research in 2007 in Frances Arnold's research group at Caltech. One of these clones is 'BM3h-B7' - one of the dopamine sensors described in Nature Biotechnology publication (2).
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Shapiro MG, Szablowski JO, Langer R, Jasanoff AP, “Protein nanoparticles engineered to sense kinase activity in MRI”, Journal of the American Chemical Society, 131(7):2484-2486, (2009)
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Shapiro MG#, Westmeyer GG#, Romero P, Szablowski JO, Küster B, Shah A, Otey CR, Langer R, Arnold FH, & Jasanoff AP, “Directed evolution of an MRI contrast agent for noninvasive imaging of dopamine”. Nature Biotechnology, 28:264–270 (2010)
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Vilanova C, Hueso A, Palanca C, Marco G, Pitarch M, Otero E, Crespo J, Szablowski JO, Rivera S, Domínguez-Escribà L, Navarro E, Montagud A, Fernández de Córdoba P, González A, Ariño J, Moya A, Urchueguía J& Porcar M, "Aequorin-expressing yeast emits light under electric control", J Biotechnology, 152(3):93-5, (2011)