Professor Jasanoff's laboratory is developing a new generation of brain imaging methods that combine the specificity of electrophysiological and optical neural recording techniques with the noninvasiveness and whole-brain coverage of functional magnetic resonance imaging (fMRI). These innovative techniques will have potentially transformative significance in neuroscience, and some will have broader impact in biology and medicine. Our own long term goal is to apply “molecular fMRI” to study neural mechanisms of behavior in alert animals. Research has included development of novel genetic and nongenetic MRI sensors for molecular targets in the nervous system, among them probes for calcium and other ions, protein phosphorylation, and neurotransmitters. We have validated several probes in vitro, and are now using some of the agents for molecular neuroimaging studies in live animals. We continue to improve our technologies and expand the range of neural targets we can detect, using a mixture of protein and genetic engineering methods and more traditional chemical approaches.
For example, when neurons become active, they rapidly take up calcium from their environment. Jasanoff hopes to visualize these rapid changes using magnetic nanoparticles that are coupled to a calcium-binding protein. In collaboration with colleagues in the MIT chemistry department, he is also developing a new class of molecules that can be engineered to accumulate inside cells and to reveal changes in the intracellular chemical environment.
Another approach is to develop indicator molecules that can be genetically encoded and thus targeted to specific cell types. Jasanoff is currently developing such an indicator for dopamine, a neurotransmitter that is depleted in Parkinson’s disease and whose effects are targeted by many psychiatric drugs as well as substances of abuse. Thus the ability to detect changes in dopamine in living animals would have many applications for the study of brain disorders. Eventually he hopes it may be possible to adapt the approach for use in human subjects, thereby providing a powerful new tool for clinical research and drug development.