Nanopipette Enables Longitudinal Genomics Studies

UC Santa Cruz professor of biomolecular engineering Nader Pourmand has developed a novel approach to study the longitudinal genomics of single cells in vivo. This approach makes it possible to investigate basic mechanisms of neurodegeneration. His team developed an innovative nanopipette technology that can be used to study the genomics of single neurons with temporal resolution.

This new technology addresses the need for an approach to study the behavior of single cancer cells or neurons within tissues, rather than in two-dimensional cultures. Such an approach could significantly improve the physiological relevance of studies on these types of cells and lead to critical new biological insights and the discovery of better therapeutics for cancer and neurodegenerative diseases.

The nanopipette provides a method for RNA retrieval that extracts just enough material (~15 picoliter) for RNA sequencing but does not impair cell function. Consequently, the nanopipette can be used to repetitively sample the same cell throughout its life. The Pourmand lab then uses novel nanogenomic sequencing approaches to measure the full array of mRNAs expressed in those tiny samples.

This technology differs from any other single-cell genomic analysis system, because it keeps the cells alive for repeated biopsy and sampling over time, while others cannot.

The Pourmand lab has used the nanopipette in the past to study the genomics of single tumor cells and has completed studies investigating the genomic basis for breast cancer cell resistance to drugs such as Taxol. They recently turned their attention to studying the genomics of single neurons in cultures derived from rodent and human induced pluripotent cells.

They also collaborate with teams at UCLA and the Gladstone Institutes to use the nanopipette to study single neurons in brain slices. These collaborations focus on investigating the unique genomic properties of dopamine neurons that degenerate in Parkinson’s disease. They will use the nanopipette to study the genomic dysfunction of nigrostriatal dopamine neurons in genetic-based animal models. These novel studies will reveal for the first time a continuous picture of the genomic changes that may cause degeneration of critical neurons involved in Parkinson’s diseases. The molecular pathways they reveal can critically impact our thinking on how to develop new drugs that may for the first time block progression of neurodegeneration.

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