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Biosciences

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Jerilyn A. Timlin, Ph.D.

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Principal Member of the Technical Staff
Bioenergy and Defense Technologies Department

(505) 844-7932 / jatimli@sandia.gov

Research Interests

Optical microscopy, spectroscopy, and spectral imaging (including fluorescence, Raman, and Fourier transform infrared [FTIR]), high-throughput imaging, superresolution techniques, multiplexed microscopy, multivariate image analysis, image preprocessing, spectral unmixing, and multivariate classification for applications in the early detection of disease/damage, immune response, signal transduction, energy transfer in photosynthetic pigments, and biomarker discovery.


Research Summary

Photomontage of research interests

My group’s research focuses on developing and applying novel analytical-imaging and multivariate-analysis tools to elucidate complex spatial–temporal relationships in biological processes.

Traditional fluorescence microscopy can locate up to three fluorescent probes in three dimensions. In single- or double-label experiments, these measurements can be interpreted in a relatively straightforward manner. However, when making multicomponent (>4) measurements, assigning accurate fluorescence contributions becomes extremely challenging due to (1) spectral bleed-through; (2) autofluorescence, which is typically broad, nondescript, and overlapped spectrally with the analytic signal of interest; and (3) the environmental sensitivity of the probe. These challenges, which effectively reduce accuracy, specificity, sensitivity, and multiplexing, greatly hinder the ability to quantify fluorescence measurements in complex biological systems.

To alleviate these limitations, my research group employs spectroscopy. We have developed both hyperspectral fluorescence line scanning and hyperspectral confocal fluorescence microscopy systems. We have also complemented total internal reflection microscopy with a unique optical design that facilitates simultaneous dual-color acquisition. In separate efforts, we have used vibrational spectroscopies (Raman and FTIR) to provide spatially resolved molecular information without the use of fluorescent labels.

The addition of a spectral dimension can result in a three-, four-, or five-dimension image data set (2–3 spatial, 1 spectral, and 1 temporal) that is beyond human visualization capabilities. We couple these high-dimensional image data sets with multivariate analysis tools to mathematically extract the underlying spectral signatures and create quantitative spatial–temporal profiles.

Our work interfaces analytical chemistry and optical physics with molecular and cellular biology and has direct impact on human health, plant science, and renewable-energy research. We work collaboratively with researchers from different scientific disciplines to tackle complex bioscience problems, including the multiplexed imaging of endogenous and exogenous fluorescence in cells and tissues, the visualization of host–pathogen interactions, the identification of molecular biomarkers for early detection of disease/damage, and membrane-specific imaging of receptor–ligand interactions.

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Current Research Projects

Multiplexed Measurements of Protein Dynamics and Interactions at Extreme Resolutions

This project was funded under the National Institutes of Health (NIH) Director’s New Innovator Award in 2009. When successful, this project will provide an unprecedented view of protein interactions in the living cell through the development of novel spectrally resolved superresolution microscopy methods.

The New Mexico Center for the Spatiotemporal Modeling of Cell Signaling

Our role in this interdisciplinary, interinstitutional program will focus on the integration of imaging and microfluidic platforms to enable single-cell experiments over a large number of cells. This aspect will provide statistical significance to the results and enable model development and validation.

From Benchtop to Raceway: Spectroscopic Signatures of Dynamic Biological Processes in Algal Communities

Funded by Sandia’s Laboratory Directed Research and Development Program, this multidisciplinary project will improve the fundamental understanding of the effect of scale on biological processes regulating algal growth and lipid production. We will combine a suite of advanced bioanalytical spectroscopic tools with genomic and standard biochemical assays to understand the effects of light and population dynamics in several species of algae that are being considered for commercial biofuels use.

Photosynthetic Antennae Research Center (PARC)

PARC is one of 46 Energy Frontier Research Centers (EFRCs) established nationally at universities, national laboratories, nonprofit organizations, and private firms by the U.S. Department of Energy’s Office of Science. A multi-institutional collaboration, PARC seeks to understand the basic scientific principles that underpin the efficient functioning of natural photosynthetic antenna systems. These principles will then be used as a basis for man-made systems to convert sunlight into fuels. Our specific work within PARC will use advanced spectral imaging and analysis methodologies to isolate fluorescent signatures from natural and bio-inspired photosynthetic pigments to increase our understanding of the spatial distribution and abundance of these critical components in the energy transfer cascade.

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Select Publications

2008 – present

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2004 – 2007

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1999 – 2003

Education

2000 PhD, Analytical Chemistry, University of Michigan, Ann Arbor, MI
1995 BS, Chemical Engineering, Geneva College, Beaver Falls, PA

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Postdoctoral Appointees Working in the Timlin Group

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Jesse Aaron
Postdoctoral Apppointee

Jesse Aaron is a 2007 Ph.D. graduate from the University of Texas at Austin Dept. of Biomedical Engineering. His interests lie at the intersection of molecular biology, nanotechnology, and advanced optical imaging. Currently, Jesse is involved in a number of projects, including an effort to understand the fundamentals of interactions between nanomaterials and living cells, as well as using total internal reflectance fluorescence (TIRF) microscopy to study the IgE receptor signaling pathway and Fas ligand exocytosis in mast cells. He is also developing an advanced hyperspectral super-resolution optical microscope that will be capable of dynamically imaging several biomolecules simultaneously in living cells at less than 40nm resolution.

Photo of Aaron Collins

Aaron Collins
Postdoctoral Apppointee

Aaron Collins is a 2010 Ph.D. graduate from the Washington University Department of Chemistry. Aaron’s Ph.D. work focused on using polarized light spectroscopies and analytical biochemistry to determine the spatial arrangement of chromophores in photosynthetic complexes where no high-resolution structural data was available. He joined the Timlin group in 2010 to investigate the distribution of natural photosynthetic complexes in living cells and how the global architecture relates to function.

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