Genetically encodable MRI contrast agents, electrically activated yeast and optogentics.
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).
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)
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)
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)