Saurabh Gupta

Dr. Saurabh Gupta

Title(s):
Affiliated lab(s):

Email: saurabhg@mit.edu
Phone: 617-715-4152
Address: E17-351

Research interest: Infectious Diseases

Title- Genetically Programmable Pathogen Sense and Destroy

Authors—Saurabh Gupta, Ron Weiss

Affiliation–Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge MA 02139

 

Worldwide, nearly 15 million people per year die from infectious diseases and they are the second biggest cause of mortality after cardiovascular diseases. Out of this 2 million deaths are caused by diarrhea alone. Pathogens responsible for these diseases have become resistant to “first-line” drugs due and second or third line drugs are much more expensive and toxic. Besides selecting for resistant bugs, one of other major drawbacks of using antibiotics is that they also kill the commensal bacteria and in turn make us more susceptible to incoming infections for example as in case of Clostridium difficile. To address such critical issues, our vision is to create a versatile, safe and effective live synthetic vaccine platform capable of adapting and responding to a large variety of target pathogens and in multiple contexts. The system should function without human intervention, and may therefore be easily deployed in remote or access-compromised environments including, for example, gastrointestinal tract or contaminated water supply systems where such pathogens often fester. Sentinel/killer vaccine may remain inert until a threat is detected, and then serve as early detection and rapid response agents.

Human body has 10 times more bacteria than their own cells and we are just beginning to understand their impact on our lives. Hence “we propose to create an alternative antimicrobial/vaccination therapy by engineering commensal cells that detect the presence of Pseudomonas Aeruginosa (major cause of urinary tract and hospital infections) and Shigella/Salmonella (biggest cause of dysentery epidemics and traveler’s diarrhea) and secrete bacteriocins/lysins that kill these pathogens with high specificity and efficiency with minimal disturbance to the natural helpful gut microbiota.

Engineering cells for detection and targeted destruction of pathogens will provide several important advantages over existing antimicrobial/vaccination strategies. Most importantly, it will offer a single integrated solution to eradicating multiple threats with an approach that is a rapid, selective, and highly sensitive. This system’s automated and high specificity reduces the possibility of resistance arising due to the administration of insufficient antibiotic dosages. This system is an effort to develop a single broad antimicrobial platform capable of analyzing environmental conditions and executing an “intelligent” response by utilizing multiple, customized treatments.