More about the science

Attempts at understanding, predicting and diagnosing disease states have faced serious obstacles as a result of the heterogeneity of in situ cell populations. By examining the behavior of individual cells in fine detail and linking preexisting states with cell fate, the Microscale Life Sciences Center is pursuing a bold new path in the study of health and disease.

Single cell studies more accurately reflect the changes of cell populations over time, frequently offering clearer results than those obtained from examination of bulk cultures. Analysis at the single cell level requires less biological material, allowing for the study of previously unculturable strains and rare cell types, which may play a vital role in the development of disease states. Nevertheless, many challenges remain. Existing single-cell techniques are often destructive or invasive to the cells under study and evaluations in real time—essential for tracking dynamic processes—are difficult to carry out.

At the MLSC, we are working to find new ways to examine multiple parameters for individual, undisturbed, living cells in real time and to correlate cellular events with genomic rearrangement and gene expression. New techniques rely on advances in microfluidics, microfabrication and microelectromechanical systems (MEMS). This comprehensive, automated and multi-tiered approach is known as a lab-on-a-chip. In addition to close monitoring of phylogenic alterations at the cellular level, such advances will ultimately allow us to carry out functional genomics and proteomics, one cell at a time.

Cellular activities such as respiration and protein expression are evaluated at the single cell level, with a focus on cell-to-cell variation—factors often missed in traditional population-averaged measurements. To date, the MLSC has performed single cell experiments with human epithelial cells, yeast, macrophages, T-cells, and bacteria, demonstrating the broad applicability of our techniques. The critical pathways to cell damage and cell death and imbalances in the cellular decision-making process are of particular concern, implicated in the disease states of cancer, heart disease, and stroke. Specifically, we have focused our attention on the processes of pro-inflammatory cell death (pyroptosis), programmed cell death (apoptosis), and avoidance of cell death (neoplastic progression). The MLSC’s bioengineering efforts include the development of microsystems with multiple sensors, environmental control, and cell manipulation capability.

Building a complete picture of the landscapes of disease by observing genomic and phenotypic variations at the level of individual cells promises to radically improve human health through the early diagnosis and treatment of illness and through the advancement of preventive strategies.