Team:UCSF

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Engineering the Movement of Cellular Robots

Some eukaryotic cells, such as white blood cells, have the amazing ability to sense specific external chemical signals, and move toward those signals. This behavior, known as chemotaxis, is a fundamental biological process crucial to such diverse functions as development, wound healing and immune response. Our project focuses on using a synthetic biology approach to manipulate signaling pathways that mediate chemotaxis in two model organisms: HL-60 (neutrophil-like) cells and the slime mold, Dictyostelium discoideum. We are attempting to reprogram the movements that the cells undergo by altering the guidance and movement machinery of these cells in a modular way. For example, can we make cells move faster? Slower? Can we steer them to migrate toward new signals?

Through our manipulations, we hope to better understand how these systems work, and eventually to build or reprogram cells that can perform useful tasks. Imagine, for example, therapeutic nanorobots that could home to a directed site in the body and execute complex, user-defined functions (e.g., kill tumors, deliver drugs, guide stem cell migration and differentiation). Alternatively, imagine bioremediation nanorobots that could find and retrieve toxic substances. Such cellular robots could be revolutionary biotechnological tools.

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CHROMATIN MEMORIES

A new tool for Synthetic Biology




Epigenetic control of gene expression

The cells of higher eukaryotes utilize chromatin state to encode "permanent" epigenetic changes in gene expression. For example, signals received by a cell during the course of development can induce the partitioning of the genome into accessible (euchromatin) and inaccessible (heterochromatin) regions that specify the fate of that cell. This epigenetic profile, in which blocks of gene are "silenced" by heterochromatin, is stably maintained and inherited by daughter cells. Thus, chromatin state provides a higher level of gene expression control that is regional (acting on many genes at once), dominant over transcription factors, ultra-cooperative (all or none), and highly stable (memory). Engineerable control over chromatin state would clearly be a powerful tool for Synthetic Biology.

We have constructed and characterized a synthetic silencing system in S. cerevisiae in which we can inducibly silence specific loci in the genome.

This foundational technology will facilitate the construction of complex genetic circuits with memory, and has potential application in the engineering of cell differentiation in higher eukaryotes.

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OUR PROJECT

Synthetic Chromatin Bit

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Aar1 Cloning System

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