Lab animals such as mice are critical tools for understanding the disease development, testing drug candidates, and devising treatments. In spite of the vast amount of knowledge generated, molecular biology assays on mice have mostly been done via ensemble measurements of the average properties of a group. However, similar to the rationale behind single molecule studies, ensemble averages often bury important details about the dynamics and ignore population heterogeneity and subsets. In this project, we will study the temporal dynamics in gene regulations during disease development (i.e. endotoxemia-induced atherosclerosis) based on """"""""single live animal experiments"""""""". We will develop ultrasensitive microfluidic ChIP-qPCR and ChIP- seq assays for testing based on tiny amounts of blood samples from mice. In principle these tests can be minimally invasive and do not perturb the state of the animal and the disease process. We will be able to conduct periodical examination of the same live mouse over the course of the disease development and understand the temporal dynamics in the transcription factor/promoter bindings and histone modifications. We believe that the single live animal data will grant unique insights into the molecular events involved in these biological processes and provide important basis for diagnosis, prognosis, drug design/discovery, and treatment strategy. Such data also most closely mimic what occurs in human patients during disease development and treatment, thus offer direct clinical relevance.

Public Health Relevance

In this project, we will use ultrasensitive microfluidic chromatin immunoprecipitation assays to study the temporal dynamics in gene regulations. We will conduct these experiments using single live mice with tiny amount of blood samples periodically extracted from them. These data will generate unprecedented details on gene regulation dynamics involved in disease development and have direct clinical relevance.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Instrumentation and Systems Development Study Section (ISD)
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Lash, Tiffani Bailey
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Virginia Polytechnic Institute and State University
Engineering (All Types)
Biomed Engr/Col Engr/Engr Sta
United States
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Cao, Zhenning; Lu, Chang (2016) A Microfluidic Device with Integrated Sonication and Immunoprecipitation for Sensitive Epigenetic Assays. Anal Chem 88:1965-72
Ma, Sai; Bryson, Bryan D; Sun, Chen et al. (2016) RNA Extraction from a Mycobacterium under Ultrahigh Electric Field Intensity in a Microfluidic Device. Anal Chem 88:5053-7
Sun, Chen; Hassanisaber, Hamid; Yu, Richard et al. (2016) Paramagnetic Structures within a Microfluidic Channel for Enhanced Immunomagnetic Isolation and Surface Patterning of Cells. Sci Rep 6:29407
Cao, Zhenning; Chen, Changya; He, Bing et al. (2015) A microfluidic device for epigenomic profiling using 100 cells. Nat Methods 12:959-62