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Opportunity at National Institute of Standards and Technology (NIST)

Developing Biomarkers for Pluripotency and Differentiation in Live Cells

Location

Material Measurement Laboratory, Biosystems and Biomaterials Division

RO# Location
50.64.41.B8005 Gaithersburg, MD

Please note: This Agency only participates in the February and August reviews.

Advisers

Name E-mail Phone
Halter, Michael michael.halter@nist.gov 301.461.0956
Plant, Anne L. anne.plant@nist.gov 301.975.3124

Description

The development of therapies and other products based on pluripotent stem cells requires control of the pluripotent and differentiated states of cells in culture. Pluripotent cells need to be expanded in culture without differentiation, and when appropriate, cells need to be differentiated into appropriate lineages. The efficiency of expansion and the completeness of differentiation is important to both efficient manufacturing and to product safety. Time-lapse microscopy of living cells allows the quantification of changes in dynamic activity of individual cells over time. We have shown that such data can provide information about fluctuations in promoter activity and can be used to predict rates of state change in cell populations. Applying these techniques to induced pluripotent stem cell (iPSC) colonies will provide a better understanding of cellular mechanics and efficiency of differentiation, and will allow systematic quantitative assessment of how conditions such as extracellular matrix and the other agents can influence differentiation. Research challenges could include creating iPSC lines with reporter constructs, designing live cell imaging experiments to assess cell response, and developing quantitative image analysis methods.

References

Sisan D.R., et al. (2012) Predicting rates of cell state change due to stochastic fluctuations using a data-driven landscape model. PNAS 109, 19262-19267

Bhadriraju K, et al. (2016) Large-scale time-lapse microscopy of Oct4 expression in human embryonic stem cell colonies. Stem Cell Research (17): 122-129

Halter et al. (2011) Cell cycle dependent TN-C promoter activity determined by live cell imaging.  Cytometry Part A. 3A: 192-202. 

Keywords:
Quantitative biology; Stem cell; Pluripotency; Differentiation; Microscopy; Image analysis; Biological variation; Predictive models;

Eligibility

Citizenship:  Open to U.S. citizens
Level:  Open to Postdoctoral applicants
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