Timothy K. Lu, MD, PhD

Email: 

Office: 

NE47-221

Phone: 

617.715.4808
Associate Professor of Biological Engineering and Electrical Engineering and Computer Science

Research-at-a-glance: 

Living Functional Materials
Synthetic Analog Computation in Living Cells
Intergrated Logic and Memory in Living Cells
Scalable Toolkits for Engineering Transcriptional Regulation in Eukaryotes
Engineered Bacteriophage Therapeutics for Antibiotic-Resistant Infection

Affiliations: 

Core Faculty Member, Synthetic Biology Center
Associate Member, Broad Institute of MIT and Harvard
Member, Research Laboratory of Electronics

Biography: 

Prof. Lu received his undergraduate and M.Eng. degrees from MIT in Electrical Engineering and Computer Science. Thereafter, he obtained an M.D. from Harvard Medical School and Ph.D. from the Harvard-MIT Health Sciences and Technology Medical Engineering and Medical Physics Program. Prof. Tim Lu joined MIT as Assistant Professor at the Department. of Electrical Engineering and Computer Science in 2010 and obtained a joint appointment at the Department of Biological Engineering in 2012.

Research: 

The Synthetic Biology Group (SBG) is focused on advancing fundamental designs and applications for synthetic biology. Using principles inspired by electrical engineering and computer science, we are developing new techniques for constructing, probing, modulating, and modeling engineered biological circuits. Our current application areas include infectious diseases, amyloid-associated conditions, and nanotechnology.

In the field of infectious diseases, SBG has focused research on bacterial biofilms, which are crucial in the pathogenesis of many clinically important infections. These biofilms are difficult to eradicate because they exhibit resistance to antimicrobial treatments and removal by host immune systems. To address this issue, SBG engineered bacteriophage to express a biofilm-degrading enzyme during infection to simultaneously attack the bacterial cells in the biofilm and the biofilm matrix, which is composed of extracellular polymeric substances. SBG has shown that the efficacy of biofilm removal by this two-pronged enzymatic bacteriophage strategy is significantly greater than that of nonenzymatic bacteriophage treatment.

To aid in the treatment of amyloid-associated condition, SBG  has used inducible genetic circuits and cellular communication circuits to regulate Escherichia coli curli amyloid production. Through this process, they demonstrate that E. coli cells can organize self-assembling amyloid fibrils across multiple length scales, producing amyloid-based materials that are either externally controllable or undergo autonomous patterning. We also interfaced curli fibrils with inorganic materials, such as gold nanoparticles and quantum dots. This work lays a foundation for synthesizing, patterning, and controlling functional composite materials with engineered cells.

Finally, SBG has been a leader in the field of nanotechnology. They have demonstrated that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. In addition, they have created a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy enables the creation of arbitrary Boolean logic functions in living cells without requiring cascades comprising multiple logic gates. By combining this work with the work focused on infectious disease and amyloid-associated conditions, the Synthetic Biology Group can definitely work towards theirs goal of developing useful solutions to real-world problems. 

Research Areas: