Engineer and biologist team receives CIRM grant to develop clear imaging of living stem cells

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Monday, April 27, 2009

By Branwyn Wagman

Electrical engineering graduate student Oscar Azucena, recipient of a University of California Graduate Research and Education in Adaptive bioTechnology (GREAT) training grant, works with Kubby and Sullivan to develop an adaptive optics microscope for dee

To understand how some individual stem cells function in living systems will require a clear view deep into the tissues where they reside--a capability that is not available today. To address this scientific need, electrical engineer Joel Kubby and molecular, cell, and developmental biologist Bill Sullivan from the University of California, Santa Cruz, received a $552,985 Tools and Technologies award from the California Institute for Regenerative Medicine (CIRM).

The Tools and Technologies Awards are intended to support work that either creates new reagents and methods for stem cell research, or that scales up existing technologies--all designed to accelerate the development of critical therapies for patients with chronic disease or injury.

"These awards represent the entry of the biotechnology industry into CIRM-funded initiatives to accelerate progress," said Alan Trounson, President of CIRM.

Kubby and Sullivan will develop a microscope system capable of delivering detailed, real-time images of living cells.

"A key component of future stem cell therapies will be the ability to track individual stem cells inside tissues. While current conventional live microscopy techniques provide excellent image resolution near the surface of a tissue, the quality of images from deep within the tissues is unsatisfactory," Sullivan said.

This is because imaging through the components inside tissues--the cytoplasm, organelles and other molecules--leads to distortions. Similar image distortions occur when looking at an object at the bottom of a pool, where motion of the water causes the image to "shimmer."

They plan to develop an improved wide-field microscope that has dynamically adjustable optics for live imaging deep within tissues that contain stem cells.

This project draws on the campus' expertise in astronomy and optics. Technical innovations recently developed by astronomers to provide clearer images of stars in space, such as using lasers and deformable mirrors, can also correct for distortions when imaging deep within tissues.

Astronomers use lasers to create reference beacons that can be used to adjust the optics in the telescope to correct for image distortions caused by changes in the atmosphere that cause the stars to "twinkle." They correct the distortions by using a dynamically deformable mirror, similar to the curved mirrors in fun houses, which make you look short or tall.

In place of lasers, Sullivan and Kubby plan to implant small flourescent beads as reference beacons near the feature of interest in the tissue. These should provide the information needed to adjust the mirrors for an undistorted view into the stem cells.

Once the new imaging system is built, they will test it by examining mechanisms of stem cell self-renewal in fruit flies. But fruit flies are just the beginning. This new imaging capability will make possible a deeper understanding of the biological mechanisms that govern human stem cell renewal, and it will prove valuable for other applications in cell and developmental biology.

Two students work with Kubby and Sullivan on this project: molecular, cell, and developmental biology graduate student Justin Crest and electrical engineering graduate student Oscar Azucena, recipient of a University of California Graduate Research and Education in Adaptive bioTechnology (GREAT) training grant.

This award brings UC Santa Cruz's total awards from the CIRM to more than $19 million distributed among five research grants, two training grants, and two facilities grants. To date, the CIRM governing board has approved 279 grants totaling close to $694 million, making CIRM the largest source of funding for human embryonic stem cell research in the world.

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