BioFrontiers’ Amy Palmer collaborated with JILA’s Ralph Jimenez to develop novel microfluidic platforms that can be adapted for a variety of time-resolved optical measurements. These new platforms allow measurements on living cells like bacteria, yeast, and mammalian cells. In addition, Palmer and Jimenez developed two instruments to support this work. One instrument measures the photophysical properties of fluorophores and another instrument measures fluorescence after perturbation.
Throughout this research project, Palmer and Jimenez have co-mentored three post-doctoral students and three graduate students. The team has published six papers and received one patent for an optically integrated microfluidic cytometer. They recently received additional $1.2 million in funding from the National Institutes of Health for their work on microfluidics-based selection for the optimization of red fluorescent proteins.
JILA researcher and BioFrontiers member, Tom Perkins, is collaborating with several researchers to improve biological atomic force microscopes, or bio-AFM, for high-resolution imaging of biological dynamics. Because there are many applications for this imaging technology, Perkins is furthering a number of single-molecule projects, including:
BioFrontiers member, Meredith Betterton is collaborating with CU-Boulder biologist, Richard McIntosh, and JILA’s David Nesbitt to understand cellular control of the spindle-assembly hierarchy that allows the cell to build the mitotic spindle. The mitotic spindle is a microtubule-based machine that organizes and moves chromosomes during the division of eukaryotic cells. Combining Betterton and McIntosh’s expertise in mitosis and cell biology with Nesbitt’s work in optics in instrumentation, the collaboration allowed this team to perform the first quantitative measurement of mitotic microtubule dynamics in fission yeast cells. It was also the first trial of fluorescence correlation spectroscopy (FCS) on tubulin molecules in any mitotic cell.
Joel Kralj, a BioFrontiers faculty member and a professor of molecular, cellular and developmental biology, studies electrical transients in bacteria and is applying this knowledge to learn how these transients also control electrical activity in human hearts and brains.
Students from the Interdisciplinary Quantitative Biology (IQ Biology) Ph.D. program with an interest in standards and technology can complete a rotation in a NIST lab, and continue their thesis research there. This option continues to be a positive recruitment element for prospective students.
The BioFrontiers Advanced Light Microscopy Core houses multiple imaging technologies that give users access to a variety of imaging tools from conventional widefield technologies to super-resolution/localization microscopies. At the heart of the facility is the Nikon A1R resonant scanning confocal system, acquired in collaboration with NIST’s Physical Measurement Lab and JILA. It is designed to provide rapid imaging of multiple fluorophores within living samples. Images can be acquired at speeds of up to 420 frames per second to capture biological events like transmission between neurons and cell signaling. In addition to the extensive suite of equipment, research experts provide support in end-to-end experiment de- sign, bringing in other core facilities and industrial partners when necessary. Because of its unique services, the facility is also used on a cost-center basis by the biotechnology industry in the state of Colorado and beyond.
Mechanical, chemical and biological cues from a cell’s microenvironment play a critical role in directing cell fate in vivo, but due to a lack of tools in bioengineering and bioimaging, we understand very little about how cells interface with their biological ecosystem in three dimensions over time The proposed Center for 4D Biosystems Engineering and Imaging will bring together a team of accomplished investigators from a national laboratory (NIST), two universities (the University of Colorado, Boulder and Stanford) and a private research laboratory (Janelia Research Center ) to image along the scale of single molecules to whole cells, design new cellular probes and reporter cell lines, synthesize new material scaffolds with in situ tunable properties and track cell processes in 3D and in real time. In addition, the Center will partner with industry to commercialize selected technologies and disseminate open technologies and methods to the external research community through short courses.