Team:MIT/Integrated Practices

• BACKGROUND
• EXPERIMENTS
  Synthetic Promoters microRNA Recombinase Proof of Concept Collaborations
• FUTURE WORK
  Circuit Design Clinical Applications
• HUMAN PRACTICES
  Parts Toolbox Accessible Protocols Integrated Human Practices Public Outreach Interlab Study
• NOTEBOOK
  Lab Notebook Parts Mammalian Parts Collection Attributions Safety
• AWARDS
  HP Silver HP Gold Integrated HP Basic Part
• TEAM

Integrated Human Practices

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June 13 - Asgi Fazleabas Visit

Asgi Fazleabas is a researcher and professor of Obsterics, Gynecology and Reproductive Biology at Michigan State University. He gave a talk to our team in early June, enlightening us about an important characteristics of endometriosis: estrogen dominance, progesterone resistance, and differing miRNA profiles. We learned progesterone resistance is, simplified, due to a lack of progesterone receptors in the cells. Here, “progesterone receptor” refers to the PGR-B isoform, the one that activates due to progesterone and binds to DNA transcription factors. This isoform is downregulated in ectopic endometrial cells. Since progesterone was a biomarker we initially designed our circuit to sense, we searched for another way for our circuit to sense a high level of progesterone present in the cell’s environment. Professor Fazleabas, doing research on a baboon model, found that in endometriosis, estrogen responsive genes are upregulated constantly, while progesterone responsive genes are always downregulated. The reason estrogen is present in abnormally high levels in ectopic cells is due to the way it’s metabolized. E2(estradiol), what we are referring to when we say “estrogen” is metabolized in the cells by a chemical reaction that needs a certain form of progesterone present to occur (research this reaction a little more so you can be more scientific). When progesterone is scarce, a buildup of unmetabolized estrogen occurs in the cell. Additionally, Asgi educated us on the fact that ectopic endometrial cells make a lot of aromatase, the enzyme that catalyzes the chemical reaction that produces E2. We thought: if we cannot sense progesterone levels in diseased cells, maybe instead we can sense for unusually high amount of estrogen?

July 11 - Meeting with Ron Weiss and Linda Griffith

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July 21 - Kevin Osteen

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July 27 - Harriet Fitzgerald

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