Team:Penn

Project Description: This year our project plans to tackle the problems of health and medicine through the lens of synthetic biology.

Part 1: Light-activated Drug Delivery

One of the most pervading diseases afflicting the lives of countless individuals is cancer. Current widespread therapies such as chemotherapy and radiation therapy are limited in their ability to serve as a highly successful cancer therapeutic due to their off-target effects. As a result, one of our projects aims to solve some of these problems of specificity through an effective synthetic system that stems from the field of optogenetics. By using a system that is controlled by light we will engineer bacteria so that it kills cancerous cells with increased specificity in three dimensions. First, the bacteria will be able to specifically target cancerous regions through the use of antibody mimetic proteins (DARPins) that bind to growth factors which are commonly found on the surface of cancer cells. Second, because the system is light-activated we will be able to increase specificity by temporally controlling the duration of the cancer treatment. Since we have the ability to determine the exposure of light to the region of the tumor, the times between doses can be easily controlled. Third, since this treatment strategy has the additional advantage of being spatially-controlled by light, the drug does not lyse normal, unaffected cells.

Part 2: Engineering microbial biofilms

Bacteria are capable of surviving on many surfaces, where they often organize into structured and highly resilient communities known as “biofilms.” Recent research has discovered that many pathogenic bacteria are capable of forming biofilms that are difficult to eradicate and even more difficult to treat. Many chemical approaches have been applied to preventing biofilm formation, especially in invasive devices such as catheters, as well as in the food processing industry. However, these devices carry the drawbacks of loss of function over time (as a result of the depletion of antimicrobial elements from the surface) and also safety concerns when used in vivo. This project seeks to investigate a biological approach rather than a chemical approach to antimicrobial surfaces. Surfaces will be colonized with a non-pathogenic, biofilm forming bacterium that would secrete antimicrobial peptides (AMP) that would inhibit subsequent colonization of the surface by pathogenic microbes. In our project, we have chosen an AMP known as lysostaphin, which selectively targets Staphylococcus bacteria, a biofilm forming genus that is a primary culprit of hospital acquired infections. Furthermore, the bacteria that form our biofilm will be programed with a bacterial “leash,” that prevents them from surviving should they become detached from the biofilm. This approach has never been attempted before in the healthcare and food production fields. Should our system function properly, it would set the groundwork for potential commercial technologies that would lead to healthier lives, and safer foods.