Team:MIT

Genetic circuit to sense endometriosis

Affecting approximately 1 in 10 women, endometriosis is a disease caused by cells similar to the endometrium of the uterus growing elsewhere in the body. These growths, called endometrial lesions, cause severe chronic pain and infertility. Because the only definitive diagnostic method is laparoscopic surgery, patients wait on average seven years between the onset of symptoms and an accurate diagnosis.

The goal of the MIT iGEM team’s project is to expedite this diagnosis process with a genetic circuit that can sense the unique biomarkers of endometriosis. Our circuit identifies whether cells are diseased by checking the cells’ miRNA profiles and by sensing progesterone resistance, a hallmark of endometriosis. This identification process can be implemented in endometrial biopsy samples, eliminating the need for surgical diagnosis. Our approach could lead to a less invasive diagnostic method, enabling earlier treatment and improving patient outcomes.

Some of our team's achievements this year include:

  1. Developed novel estrogen and progesterone inducible synthetic mammalian promoters through bottom-up promoter engineering. These constructs could resolve the changes in estrogen and progesterone signaling characteristic of endometriosis

  2. Characterized the functionality of a miRNA sensing platform in TERT immortalized human endometrial stromal cells (tHESC). We are one of the first to characterize changes in miRNA activity in the cell line with and without estrogen.

  3. Characterized the functionality of a serine integrase (TP901) in a mammalian cell line. Recombinases like TP901 downstream of a tunable l7Ae - kturn system that we implemented could help process input from our estrogen, progesterone, and miRNA sensors and adjust output as per a patient's needs.

  4. Transfected larger 4 to 5 transcriptional unit genetic circuits that cascaded our devices together in order to explore how our sensors interact with one another.



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