Quantitative imaging application to gut and ear cells are reported in 2 Nature papers

(Press-News.org) BOSTON, MA -- From tracking activities within bacteria to creating images of molecules that make up human hair, several experiments have already demonstrated the unique abilities of the revolutionary imaging technique called multi-isotope imaging mass spectometry, or MIMS, developed by researchers at Brigham and Women's Hospital (BWH). MIMS can produce high-resolution, quantitative three-dimensional images of stable isotope tags within subcellular compartments in tissue sections or cells.

With its use of stable isotopes as tracers, MIMS has opened the door for biomedical researchers to answer various biological questions, as two new studies have demonstrated. These studies looked at the use of MIMS in tracking cell division in intestinal stem cells, lipid turnover in Drosophila flies, protein turnover in ear cells, and opened the way to human application by detecting the formation of new white blood cells. Both studies will be published in Nature online on January 15, 2012 and in print on January 26, 2012.

In the first study, researchers used MIMS to test the much debated "immortal strand hypothesis" which claims that as stem cells divide, the older template DNA remains together in a stem cell, as the newer DNA is passed to cells that differentiate forming the digestive lining of the small intestine.

By tagging DNA with stable isotope tracers, researchers tracked DNA replication as cells divided. They found that in any situation DNA segregation was random, thereby disproving the immortal strand hypothesis.

The research opened another door by studying lipid metabolism within single lipid droplets of the fat body and of the central nervous system of Drosophila larvae. The researchers were also able to translate their work to humans. In a pilot study, they used MIMS to successfully track the formation of new white blood cells after administering isotope tracers in a healthy human volunteer.

The second study demonstrated that protein turnover in stereocilia in the inner ear is extremely slow contrary to the prevalent belief in the field. Stereocilia are hair-like projections found in cells of the inner ear that are responsible for hearing and maintaining balance. Using MIMS, researchers saw that protein turnover was very slow throughout the stereocilia, except the tip at the location of the mechanoelectrical transduction apparatus.

MIMS was created by developing several tools—an ion microscope/secondary-ion mass spectrometer, labeling with stable isotopes, and quantitative image-analysis software. Unlike other imaging technologies, MIMS does not require staining or the use of radioactive labeling. MIMS enables researchers to conduct experiments with safe, non-toxic stable isotopes, which are naturally occurring components of all living matter.

### Claude Lechene, MD, professor in the Division of Genetics, Department of Medicine and director of the National Resource for Imaging Mass Spectrometry (National Institutes of Health), was the senior study author for both studies.

The first study was a collaboration among BWH researchers and Alex Gould, PhD, and Andrew Bailey, PhD from the Medical Research Council National Institute for Medical Research (UK). BWH researchers a part of the first study are lead study author Matthew Steinhauser, MD, Division of Cardiovascular Medicine, Department of Medicine; Samuel Senyo, PhD, Division of Cardiovascular Medicine, Department of Medicine; Christelle Guillermier, PhD, Division of Genetics, Department of Medicine; Todd Perlstein, MD, Division of Cardiovascular Medicine, Department of Medicine; and Richard Lee, MD, Division of Cardiovascular Medicine, Department of Medicine.

The second study was a collaboration among BWH researchers and researchers from the following institutions: Duan-Sun Zhang, PhD (lead study author) and Valeria Piazza, PhD in the laboratory of David Corey, PhD (HHMI investigator), Department of Neurobiology, Harvard Medical School. Other researchers that contributed to the study include Benjamin Perrin, PhD and James Ervasti, PhD both from the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota and Agnieszka Rzadzinska, MD, and Haydn Prosser, PhD, of the Wellcome Trust Sanger Institute (UK). BWH researchers a part of the second study are Joseph Collin Poczatek, technical research assistant and Mei Wang, senior research assistant both in the Division of Genetics, Department of Medicine.

Research for the first study was supported by the National Institutes of Health, Ellison Medical Foundation, Human Frontier Science Program, American Heart Association, Future Leaders of Cardiovascular Medicine, Medical Research Council, Harvard Stem Cell Institute, and Cambridge Isotope Laboratories.

Research for the second study was supported by the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering, National Science Foundation Division of Integrative Biology and Neuroscience, and the Wellcome Trust.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), http://www.brighamandwomens.org/research, BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit http://www.brighamandwomens.org.