The Molecular Atlas Project: Direct Observation and Quantification of Spatially Heterogeneous Proteomic Data in Healthy, Cancerous, and Therapeutically Treated Tissue. The Molecular Atlas Project (MAP) combines wetware, hardware, and software for seamless proteomic mapping, navigation, and exploration across seven orders of magnitude in length from single molecules to entire tissues. The most significant intellectual contribution of MAP is to solve the competing interests between super-resolution microscopy, which visualizes molecular-scale details, and spatially contextualized information, which strives for tissue-scale understanding. Successful completion of the aims will therefore offer a new approach to biological imaging, new discoveries in breast cancer, and new open-access resources containing proteome data at the sub-cellular level, for any cell in an entire centimeter sized histological tissue section. The relevance for cancer biology is the development of a discovery-oriented tool for basic cancer science, giving unprecedented levels of information on cell-specific heterogeneity. This project is made possible by technology innovations that combine the super-resolution imaging capabilities of multiplexed DNA-PAINT with automated image acquisition and big data management strategies, thus making vast improvements over current state-of-the-art methods that emphasize either super-resolution or tissue-scale data. Instead of this either/or scenario, MAP does both. While conducting my research, I will be mentored by my postdoctoral advisor Dr. Peng Yin, who is a highly regarded expert in DNA nanotechnology, and will utilize an ongoing collaboration with Dr. Joan Brugge, a highly recognized leader specializing in breast cancer research at the Harvard Medical School.
The aims of this proposal are carefully crafted to leverage my expertise in physics and instrumentation, while simultaneously cultivating a program of hands-on experience and training in cancer biology. Despite having minimal prior exposure to this field, my strategy allows me to make immediate contributions in the short-term, while simultaneously investing in a knowledge base for a long-term research career in the physical aspects of cancer biology. Performing this research at the Wyss Institute for Biologically Inspired Engineering at Harvard University offers critical advantages, as the institute's environment encourages, fosters, and supports technology development and translation. Moreover, the local proximity to numerous hospitals and medical institutions give unparalleled access to cancer researchers and potential collaborators.

Public Health Relevance

Just as Google Maps revolutionized the way we view and interact with geography, the Molecular Atlas Project aims to revolutionize the way we view and interact with biological tissues. This combined wetware, hardware, and software approach to imaging is a proteome visualization pipeline for length scales ranging from the molecular to the macroscopic. Completion will enhance our understanding of the human body and its ailments with unprecedented detail, while laying a foundation for next generation therapeutics - try it yourself and explore the possibilities at

National Institute of Health (NIH)
National Cancer Institute (NCI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Mcguirl, Michele
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Harvard Medical School
Internal Medicine/Medicine
Schools of Medicine
United States
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