Many applications of induced pluripotent stem cell (iPSC) technologies will require the differentiation of cells into specific lineages. Current protocols for differentiation are described as static recipes where changes to the culture conditions occur at fixed time points. In practice, the optimal timing of different processing steps will likely be specific to each new cell line and culture system. This research project aims to identify measurements that can provide feedback to guide processing parameters in real time. Ideal measurement approaches will be minimally-invasive so that the stem cell culture is not perturbed. Design of experiments will be used to systematically evaluate how changes to culture conditions influence differentiation outcomes. Measurement approaches could include time lapse imaging of live cells by transmitted light, quantitative phase, or surface plasmon resonance microscopy; image analysis; the application of fluorescent protein reporter cell lines; and flow cytometry. Statistical analysis will be used to identify and critically evaluate measurements that appear most informative for scheduling the steps of a differentiation process.

 

Reference

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

 

key words

Bioengineering, Quantitative biology; Stem cell; Pluripotency; Differentiation; Microscopy; Image analysis; Cardiac myocytes; Precision medicine;

Citizenship:  Open to U.S. citizens

Level:  Open to Postdoctoral applicants