Biomolecular Engineering of Reporters and Sensors for Noninvasive Imaging of Cellular Function

Abstract

Many important biological processes – ranging from simple metabolism to complex cognition – take place deep inside living organisms, yet our ability to study them in this context is very limited. Technologies such as fluorescent proteins and optogenetics enable exquisitely precise imaging and control of cellular function in small, translucent specimens using visible light, but are limited by the poor penetration of such light into larger tissues. In contrast, most non-invasive technologies such as magnetic resonance imaging (MRI) and ultrasound – while based on energy forms that penetrate tissue effectively – lack the needed molecular precision. Our work attempts to bridge this gap by engineering new molecular technologies that connect penetrant energy to specific aspects of cellular function in vivo. In this talk, I will describe molecular reporters for non-invasive imaging using MRI and ultrasound developed by adapting and engineering naturally occurring proteins. These proteins have physical properties, such as paramagnetism or self-assembly into hollow nanostructures, that allow them to be sensitively detected with MRI and ultrasound. By engineering them at the genetic level, we have adapted these natural constructs into noninvasive molecular reporters of biological processes ranging from gene expression to chemical neurotransmission and metabolism. In addition, I will describe recent work on the use of penetrant forms of energy to control cellular function within the body.