Team:UCSF/Project

Our team was inspired by the use of robots which perform tasks that would otherwise be difficult to accomplish. For example, the Mars rovers allow us to make observations and conduct physical experiments in harsh, remote locations otherwise inaccessible to humans. In many ways, the human body represents unexplored territory on a different scale. For example, we may understand many aspects of human disease. However, certain markers of disease are extremely difficult to detect (e.g., primary tumors) and treatment of disease can be hampered by the impracticality of performing invasive surgeries.

The "holy grail" of nanomedicine would be to develop microscopic robots that could travel anywhere in the body and perform complex, user-defined tasks. Such devices would have several key advantages over traditional, small-molecule therapies:


 * They could home to specific locations in the body (minimize off-target effects)
 * They could make decisions based on their external environment
 * They could perform more complicated functions

While the idea of microscopic, therapeutic robots may seem far-fetched, there are examples of such machines in nature. For example, neutrophils (a type of white blood cell) are capable of:


 * Detecting and homing to a wide range of chemical signals, at times localizing to very specific sites of inflammation
 * Triggering a variety of different pathways (extravasation, phagocytosis, apoptosis) in response to external signals
 * Navigating through different types of barriers (endothelial tissue, blood-brain barrier, etc)

Taking cues from nature, we were interested in harnessing or hijacking the function of complicated, natural cellular robots such as neutrophils to perform therapeutically useful tasks. In other words, we wanted to use neutrophils (or similarly motile cells) as a chassis for engineering. Minimally, we wanted to control how and when these cells move. Over the course of the summer, were were able to:


 * Control the NAVIGATION system of our cells (alter what the cells pursue, how strong a signal they require)
 * Control the SPEED of our cells (engineer accelerators and brakes)
 * Deliver a PAYLOAD with our cells

Our efforts toward these goals are described in the remainder of this site. Throughout our project, we worked with two model organisms: HL-60 (neutrophil-like) cells and Dictyostelium discoideum, a soil-dwelling amoeba that feeds on bacteria. Both cell types are common models for the study of chemotaxis (directed migration toward chemical signals), and each has its distinct advantages with respect to studying specific questions.

PROJECT SUMMARY

Part 1 - Engineering NAVIGATION

Part 2 - Engineering SPEED

Part 3 - Carrying a PAYLOAD

Part 4 - Future Application