Gene regulation is a logistic challenge for widely arborized neurons that need to follow local cues during their outgrowth, maintain regional homeostasis, and quickly respond to synaptic inputs at sites a great distance away from their cell body. Local mRNA storage and protein synthesis have been shown to be important for axonal guidance, synaptogenesis, and synaptic plasticity consistent with hypotheses on quasi-autonomous local protein synthesis in neurons. It has however remained technically challenging to identify the kinetics and function of local mRNA translation and understand the parameters of its regulation. In this project, we thus seek to develop a more efficient genetic method for spatiotemporal regulation of specific mRNA levels. This will be pursued by a combination of protein engineering and live cell imaging. The technique aims at enabling systematic analyses of regulation and function of local protein expression and may find broader applications in tissue engineering and interventional studies.

... coming soon

Westmeyer GG, Emer Y, Lintelmann J, Jasanoff A (2014). MRI-based detection of alkaline phosphatase gene reporter activity using a porphyrin solubility switch. Chem Biol 21(3):422-9. 

• Shapiro*, M. G., Westmeyer*, G. G., Romero, P. A., Szablowski, J. O., Kuster, B., Shah, A., Otey, C. R., Langer, R., Arnold, F. H., and Jasanoff, A. (2010) "Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine", Nat Biotechnol 28: 264-270; * contributed equally

• Westmeyer, G. G., Durocher, Y., and Jasanoff, A. (2010) "A secreted enzyme reporter system for MRI", Angew Chem Int Ed Engl 49: 3909-3911

• Westmeyer, G. G., and Jasanoff, A. (2007) "Genetically controlled MRI contrast mechanisms and their prospects in systems neuroscience research", Magn Reson Imaging 25: 1004-1010

• Shapiro, M. G., Atanasijevic, T., Faas, H., Westmeyer, G. G., and Jasanoff, A. (2006) "Dynamic imaging with MRI contrast agents: quantitative considerations", Magn Reson Imaging 24: 449-462

• Westmeyer, G. G., Willem, M., Lichtenthaler, S. F., Lurman, G., Multhaup, G., Assfalg-Machleidt, I., Reiss, K., Saftig, P., and Haass, C. (2004) "Dimerization of beta-site beta-amyloid precursor protein-cleaving enzyme", J Biol Chem 279: 53205-53212

• Lichtenthaler, S. F., Dominguez, D. I., Westmeyer, G. G., Reiss, K., Haass, C., Saftig, P., De Strooper, B., and Seed, B. (2003) "The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1", J Biol Chem 278: 48713-48719

• Fluhrer, R., Multhaup, G., Schlicksupp, A., Okochi, M., Takeda, M., Lammich, S., Willem, M., Westmeyer, G., Bode, W., Walter, J., and Haass, C. (2003) "Identification of a beta-secretase activity, which truncates amyloid beta-peptide after its presenilin-dependent generation", J Biol Chem 278: 5531-5538

• Fluhrer, R., Capell, A., Westmeyer, G., Willem, M., Hartung, B., Condron, M. M., Teplow, D. B., Haass, C., and Walter, J. (2002) "A non-amyloidogenic function of BACE-2 in the secretory pathway", J Neurochem 81: 1011-1020