medicine photo

Translation

Our final thrust transitions from development of quantum sensors and imaging platforms to using these tools to address both fundamental and applied questions in biology and medicine. The goals of this thrust are to uncover previously unmeasurable properties and dynamics in nanoscale environments, determine spatial correlations and patterning of these features across living cells or tissue at larger scales, and understand how all of the above influences larger scale biological and health outcomes. To hasten widespread adoption of quantum technologies for biological sensing, we will also make the most promising and advanced sensing and imaging platforms widely available to other researchers through core facilities at UChicago.

Many subcellular objects, including certain organelles, compartments, complexes, and synapses, are currently minimally accessible (even inaccessible) to detailed study; nanoscale features, molecular crowding, and physical barriers confound or block classical imaging and sensing approaches. In particular, study of membranes, interfaces, and junctions, where dissimilar regions interact, will be greatly assisted by the integration of the quantum sensors and the correlated and/or delocalized sensing106 approaches enabled by quantum technologies, so these inaccessible regions may be sensitively probed.

Approach

  • Task 1: Arguably, the most important, complex, dynamic, and least classically tractable measurements in cell biology are those that seek to characterize the nanoscale, heterogeneous nature of interfaces between different biological compartments. Cellular interfaces and junctions serve as critical communication and interaction sites for chemically discrete environments. At these contact sites between cells, organelles, and other structures, physical, chemical, and electrical dynamics and fluxes provide transport and signaling pathways that dictate the interplay of all intra- and extra-cellular processes, and are directly responsible for the exquisite specificity, broad range, and delicately maintained balance of signaling outcomes. These sites are always spatially restricted and crowded with molecules, and their composition may change dynamically. Conventional methods generally lack the sensitivity and precision to report on the nanoscale details of processes at biological interfaces and junctions. We will use the quantum probes we have developed, in conjunction with the protocols and modifications for biocompatibility developed within NSF QuBBE, and novel correlative imaging technologies, to image the local environments, the charge and chemical fluxes, and the dynamic changes in the organization of cellular interfaces and junctions. Starting with single ion channels in cell membranes, we will examine systems at the cell membrane, at extracellular interfaces and junctions, and at intracellular interfaces and junctions.
  • Task 2: Medical outcomes could be better predicted and managed with improved information on the heterogeneous metabolic, signaling, and drug efficacy that may vary from cell to cell within e.g., diseased tissue or a tumor. NSF QuBBE will be positioned to transfer technologies that map and image charge, fields, and metabolites in cells to biomedical challenges that stem from intracellular chemical and electromagnetic variation such as those involving cellular metabolism, signaling, and energy production and transport. This effort will combine the different sensors developed in NSF QuBBE with specific biomedical challenges that require detailed information on how chemical fluxes and fields are altered in diseased states. The ability to monitor these conditions in distal parts of a cell or across different cells in a tissue will directly link nanoscale indicators with their medical relevance.
  • Task 3: UChicago maintains core facilities open to the public and the greater scientific community on a recharge basis. These facilities include cryo-EM, NMR, MRI, TEM, STEM, sub-diffraction limited microscopy, fluorescence imaging, and x-ray facilities. NSF QuBBE will build off these existing capabilities to create novel sensing and imaging modalities that will be immediately available to the scientific community and to members of the center.