Many of life’s failures are experienced by people who did not realize how close they were to success when they gave up.” Thomas Edison
Chelsea Anorma graduated from the University of California, Irvine with a B.S. in Chemistry in June 2014. She began her graduate career in the Department of Chemistry under the division of Chemical Biology at the University of Illinois at Urbana-Champaign in Fall 2014. She began work at the Chan lab at the end of that year. Chelsea is currently working on genetically-encoded and small-molecule based probes for photoacoustic imaging. In the future, Chelsea would like to work in academia.
Ca2+ is an essential element that is involved in signal transduction, where it acts as a second messenger to exert control over membrane excitability, synaptogenesis, and neurotransmission. However, misregulation of Ca2+ is linked to a variety of diseases such as Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS). In this regard, a majority of intracellular Ca2+ is tightly sequestered in the mitochondria and endoplasmic reticulum. Unbound cytosolic Ca2+, defined as “free Ca2+”, is only in the 0.1 µM range; however, rapid release from organelle stores can be triggered by molecules such as ATP which can temporarily elevate levels by up to 100-fold. To visualize and study these changes, genetically encoded Ca2+ indicators (GECI) are very promising due to their ability to be targeted to specific types of neurons and to be used in chronic measurements over weeks or months. For in vivo applications, GECI must absorb and emit in the near infrared (NIR) region (650-900 nm) to curtail issues with light scattering and absorption by endogenous biomolecules. Currently, the furthest red-shifted GECI absorbs at 610 nm. To push this limit, we have developed the first-generation GECI based on an infrared fluorescent protein and the calmodulin/M13 and troponin C calcium binding domains. Since our GECI exhibits a strong absorbance band in the NIR region it can also be used for photoacoustic (PA) imaging which will allow us to perform deep tissue imaging in the cm depth range. Future work includes improving the dynamic range and response time, as well as to apply the system to neuronal culture and whole animal imaging.