Stanford’s Quake Lectures at NIBIB Council|
Dr. Stephen Quake, the Lee Otterson professor of bioengineering, physics and applied physics at Stanford University, recently gave the fourth annual Lopez lecture at NIBIB’s September council meeting. He described how he, his colleagues and students have employed “precision measurement in medicine” to develop and exploit the properties of microfluidic chip and sequencing technologies—creating paradigm shifts in crystal formation, single cell genomics and non-invasive prenatal diagnosis.
One of the first successes of microfluidics was that the physical properties of reagents at nanoliter volumes allowed crystal formation of important biological proteins that would not crystallize under standard conditions. The study of the structure of these proteins dramatically advanced our knowledge of their roles in human health and disease and the subsequent development of medical treatments.
Another breakthrough enabled by microfluidics was single cell genome analysis. One of the initial studies tracked gene expression as cell types differentiated in the developing lung to create alveoli. Large sets of transcripts were found that defined each cell type of the differentiating lung.
Another early study used microfluidics and single cell genomic amplification to follow the changing patterns of gene expression in individual clonal lines of cells in childhood acute lymphoblastic leukemia. The researchers tracked patterns of emergence of mutated genes in individual cells of the tumor population. Each patient presented with distinct patterns of combinations of mutated genes. However, the analysis revealed commonly mutated genes in many clones, suggesting common targets for therapies despite the polyclonal nature of the disease.
Quake concluded with examples of how the lab adapted single molecule sequencing and precise counting of amplified molecules of cell-free DNA in blood to eliminate risky, invasive diagnostic procedures.
Quake’s take-home message is that nearly all the technologies he described have become commercially available and have significantly improved public health.—Thomas M. Johnson