Computer engineering enables researchers to program electronic systems that carry out designated, intelligent tasks. What if we could program biological circuits in living cells to perform similar computational functions inside our body? Imagine smart probiotics that, when swallowed, would swim inside a patient’s gut and detect any signs of inflammatory bowel diseases -- or, customized antimicrobials that can be rapidly engineered to overcome antibiotic-resistant bacteria. Inspired by electrical engineering and computer science principles and his training in clinical medicine, Dr. Timothy Lu, Associate Professor of Biological Engineering and Electrical Engineering at the Massachusetts Institute of Technology, has established foundational design principles for constructing, probing, modulating, and modeling engineered biological circuits in living cells. The ability to program living cells can enable breakthrough technologies for diagnostics and therapeutics for a wide range of human diseases.

Dr. Lu’s Synthetic Biology Group is focused on understanding how biological systems are naturally built, and using this insight to program cells by modifying their underlying “software” encoded in DNA. An electrical engineer as well as a medical doctor, Dr. Lu carries expertise in both technological and clinical settings and values interdisciplinary collaborators like physician partners to tackle challenging human diseases such as cancer, inflammatory bowel disease, neurodegenerative diseases, and heart disease. By understanding basic disease biology and crafting targeted therapies, Dr. Lu develops novel diagnostic and therapeutic technologies and has founded several companies to push these technologies towards real-world applications. Ultimately, Dr. Lu hopes to translate other current projects into clinical applications, conducting a truly translational research agenda to help patients fight various diseases.

Current research includes:

• Foundational Work on Biological Systems: Currently, there isn’t a clear understanding of how biological systems are wired to carry out all of their sophisticated functions. Dr. Lu is thus developing technologies to decipher what the underlying logic and design rules are for natural biological systems in very high throughput, and to program sophisticated genetic circuits that can carry out artificial tasks -- such as memory, mathematical operations, and logic. By implementing computational functions in cells, Dr. Lu will be able to create new diagnostics and therapeutics for a wide range of clinical applications.
• New Strategies for Tackling Antibiotic-Resistant Bacteria: Antibiotic resistance is a major worldwide problem that is steadily worsening, but fewer and fewer new antibiotics are available. Because current antibiotics have a very broad spectrum, they kill both good and bad bacteria, leading to side effects and accelerated evolution of antibiotic resistance. On this front, Dr. Lu is building precision antimicrobial agents as personalized and effective therapeutics against antibiotic-resistant bacteria.
• Engineering Smart Bacteria: Dr. Lu and his lab are designing smart probiotics that can be consumed by patients, after which the probiotics transit through the gut where they can non-invasively detect and treat diseases within the patient. For example, people with inflammatory bowel disease often don’t know when their next flares will happen, but engineered probiotics could help provide early harbingers of disease and also deliver proactive treatment. This platform is broadly applicable to a wide range of human diseases, including the detection and treatment of cancer, infectious diseases, and inflammation.
• Programming Smart Cell Therapies: Most existing therapies are chemical drugs, antibodies, and proteins, but for many complex diseases like cancer, autoimmune diseases, and neurodegeneration, it is not a single factor that causes the disease but rather a compilation of many sophisticated modalities. Therefore, in order to achieve highly effective therapies, researchers must create multifactorial therapeutics that can address malfunctioning human systems. Dr. Lu and his team are engineering new types of gene therapies and human cell therapies with the tools of synthetic biology to tackle this hurdle. Dr. Lu aims to program artificial gene circuits that can sense complex cellular environments and disease states and respond by generating effective and combinatorial therapeutics. The platform technologies being developed in this research thrust are being applied to a wide range of areas, including cancer, neurodegenerative diseases such as Parkinson’s disease, autoimmune diseases, and heart diseases.