Jerilyn Timlin

Distinguished Member of the Technical Staff

Portrait of Jerilyn Timlin

and spectroscopic-based tools in conjunction with multivariate image analysis to understand the fundamental spatial-temporal relationships that govern complex biological processes. Her 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. She has initiated and collaborated with researchers from different scientific disciplines to tackle complex problems in biodefense and bioenergy, including multiplexed imaging of endogenous and exogenous fluorescence in plant and animal cells and tissues, visualization of host-pathogen interactions, nanoparticle uptake and trafficking, receptor ligand interactions, and identification of molecular biomarkers for early detection of disease and cellular response to changing environmental conditions.

Education

Bachelor’s Degree: Chemical Engineering, Geneva College, Beaver Falls, PA (1995)

Doctoral Degree: Analytical Chemistry, University of Michigan, Ann Arbor, MI (2000)

Postdoctoral Fellowship: Analytical Chemistry, Sandia National Laboratories (2002)

Research Interests

Timlin’s research focuses on developing and applying novel analytical-imaging and multivariate-analysis tools to elucidate complex spatial-temporal relationships of a variety of biomolecules that drive key biological processes.The work in our lab crosses traditional boundaries of chemistry, physics, and biology and often covers multiple spatial scales from single molecules on up to single cells, communities, and tissues. A main component of our work is spectral imaging – a method whereby spectrally resolved information is obtained at every two-dimensional pixel or three dimensional voxel. I have been developing and applying various spectral imaging technologies (also called chemical imaging) since my graduate work which pioneered the use of hyperspectral Raman microscopy with near-infrared excitation to elucidate the dynamic chemical composition of bone without the use of labels. Most recently, my group has employed both hyperspectral Raman and fluorescence microscopy to a variety of applications looking at single molecules to intact tissue, including the visualization of subcellular pigment distribution in photosynthetic organisms such as cyanobacteria and green algae (Figure 1 at right).

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. For this reason we utilize sophisticated multivariate analysis tools to mathematically extract the underlying spectral signatures and create quantitative spatial-temporal profiles of biomolecules.

In keeping with the multicolor theme, Timlin’s lab has developed multi-color, optical super resolution capabilities. Building from our unique capabilities in dual-color, video rate, total internal reflection fluorescence (TIRF) microscopy, we have constructed a simultaneous, dual-color single molecule, stochastic optical super-resolution (STORM) microscope. With spatial resolutions approaching those of electron microscopy (~30-40 nm), this technology is opening our eyes to a variety of biological processes never before seen. For example, Figure 2 highlights receptor reorganization at the membrane during immune response.

Timlin’s 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.

Hyperspectral confocal Raman image of carotenoids and achlorophyll in living Haematococcus pluvialis cells. Upper panel: component spectra. Lower panel: pigment localization, pseudo-colored corresponding to spectra in upper panel. Figure generated by Aaron Collins in collaboration with Thomas Beechem, and Howland Jones at SNL and Dr. Qiang Hu's group at ASU.

Figure 1 (top right): Hyperspectral confocal Raman image of carotenoids and chlorophyll in living Haematococcus pluvialis cells. Upper panel: component spectra. Lower panel: pigment localization, pseudo-colored corresponding to spectra in upper panel. Figure generated by Aaron Collins in collaboration with Thomas Beechem, and Howland Jones at SNL and Dr. Qiang Hu’s group at ASU.

Figure 2 (bottom left): Nanoscale organization of Toll-like Receptor 4 (TLR4) and E. coli lipopolysaccharide (LPS) at the plasma membrane of mouse macrophage cells as visualized with simultaneous, dual-color stochastic optical reconstruction microscopy (STORM). Figure generated by Jesse Aaron, work in collaboration wtih Bryan Carson at SNL.

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.

Analyzing and Understanding of Transporters to Control Lignin Transformation into Fuel

The overall goal of this project is to understand the fundamental relationships that govern lignin transport in order to control transport in a way that will provide an increase in the range and kinetics of transport into cells. Timlin is developing analytical tools for assessing lignin uptake and kinetics in bulk and at the single cell/single molecule level. Combining experimental measurements with computational modeling, she hopes to identify the types of transporters that are active on lignin and their substrate specificity as well the kinetics of lignin transport in natural and engineered hosts.

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. Timlin’s 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.

Awards, Honors, and Memberships

Memberships

  • Editorial board, American Journal of Molecular and Cellular Biology (2011)
  • Member, Optical Society of America (2011) Member, Microscopy Society of America (2007)
  • Member, Coblentz Society (2001) Member, Society for Applied Spectroscopy (1998)
  • Member, American Chemical Society (1992)

Awards and Honors

  • SNL Distinguished Mentorship Award (2016)
  • SNL Employee Recognition Award: Individual Values, Ethics, and Integrity (2013)
  • Outstanding Women at Sandia National Laboratories winner (2011)
  • KNME Science Café Speaker (2011)
  • NIH New Innovator Award (2009)
  • R&D 100 Award Winner “Hyperspectral Confocal Microscope” (2009)
  • Sandia National Laboratories Emerging Leaders Program (2008)
  • American Chemical Society- Div of Analytical Chemistry Fellowship (1999-2000)
  • Graduate Student Council in Chemistry President (1998-1999)
  • Student panelist for Office of Conflict Resolution (1997-1999)
  • GAANN (Graduate Assistantship in Area of National Need) Fellow (1995-1998)
  • Graduate Student Council in Chemistry (1995-1997)
  • Presidential Scholar, Geneva College (1991-1995)

Selected Patents

  • US Patent. No.:  US 8,686,363 B1 “Hyperspectral Stimulated Emission Depletion Microscopy and Methods of Use Thereof”, Jerilyn A. Timlin and Jesse S. Aaron, Awarded April 1, 2014.

Selected Book Chapters

  • Timlin, JA, Collins, AM, Shumskaya, M, Wurtzel, ET, Beechem, TA, “Localizing and Quantifying Carotenoids in Intact Cells and Tissues” in Carotenoids. Cvetkovic, D and Nikolic, G. InTech:Rijeka, 2017, Ch. 03.
  • Haaland, DM, Jones, HDT and Timlin, JA, "Experimental and data analytical approaches to automating multivariate curve resolution in the analysis of hyperspectral images " in Resolving Spectral Mixtures, Ruckebusch, C, editor(s). Elsevier: Amsterdam, 2016, 381-406.
  • Anthony S, Carroll-Portillo A and Timlin JA, "Dynamics and interactions of individual proteins in the membrane of single, living cells " in Single Cell Protein Analysis. Singh, AK and Chandrasekaran, A, editor(s). Springer New York: 2015, 185-207.
  • Chen W, Han D, Li Y, Jones HDT, Timlin JA, Hu Q, Semi-Quantitative and Absolute Quantitative Analyses of Biochemical Composition of Microalgae. In Handbook of Microalgal Cultures – Second Edition. Hu R, (Ed.), Wiley-Blackwell, 2013.
  • Aaron JS and Timlin JA “Advanced Optical Imaging of Endocytosis,” in Molecular Recognition of Endocytosis, B. Ceresa (Ed.), InTech, 2012.
  • Timlin JA, "Scanning microarrays: Current methods and future directions," In DNA Microarrays, Part B: Databases and Statistics. Kimmel A, Oliver B, editors. Academic Press: New York, 2006: 79-98.

Publications