Team:NTU-Taida

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== Project Description: Bio-Molecular Synthetic Chain For Human Diseases ==
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== PepdEx: Smart Peptide-Based Therapies ==
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*Rapid development of genetic technology applied in a wide spectrum of areas, agriculture, environmental protection, anti-microbial, synonymous to biofouling. The basic concept is simple, that is how to manipulate our microbes to express and secret certain chemicals. As a medical-based lab, we try to manipulate the attractive microbial production technology into our project design for targeting human diseases.<br />
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*Microbial biotechnology has applications in a wide spectrum of areas, from agriculture, environmental protection to biofuels. The original scheme is simple, for instance manipulate microbes to produce certain chemicals. As a medical-based team, we aim to design microbes to target human diseases. The ultimate goal is to use microbes as a general platform to do complex calculations that respond to conditions in human body, and then administer smart peptide-based therapies.<br />
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*As E. coli based microbial secretory systems, we found it efficient to secret synthetic long peptides, rather than a protein. Synthetic peptides have multiple roles in human diseases, ranging from anti-cancer, anti-allergy vaccine, neuro-endocrinology supplement. However, different therapeutic trials of synthetic peptides require different circuit design for secretion, especially in its diverse biochemical rhythm from which we simulates its natural secretory pattern or therapeutic regimen of desire.<br />
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*We will first use anti-obesity as a proof-of-principle application to this approach. Non-pathogenic E. Coli will live in the intestines and serve as a device to sense the presence of fatty acids, and as an output secret synthetic GLP-1 peptide to suppress the appetite. Appropriate signal peptide and Penetratin will be used to facilitate peptide secretion and intestinal uptake, respectively. Since the intestine is a highly fluctuating environment, we will incorporate a two-filter circuit with anti-noise function, so that the system only responds to sustained stimulus. In addition, due to burden effect bacteria with artificial plasmids will be gradually lost from the population without selection pressure; plasmid segregational instability will also introduce undesirable alterations to the final function for systems encoded in multiple plasmids (as in our case). <br />
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*In our project, we take three peptide for examples, GLP-1, which is a neuro-endocrine for metabolic control, and synthetic long peptides for anti-cancer vaccine and anti-allergy, and by using mathematical and computation engineering, we design circuits respectively, try to understand its effect either intercellular or in multicellular structures. In addition, we also bring partition system to our circuit, which largely circumvent the instability of plasmid in engineered bacterial production secretion system. Hence, we are expecting to bring a novel and stable delivery system for synthetic peptides targeting human diseases.<br />
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*To circumvent this, we also incorporate plasmid stabilization modules including partition system and multimer resolution system. With this general concept we will also explore other pieces of human disease with alternative circuit designs, for instance with an oscillator circuit we can periodically deliver synthetic peptides based on natural secretory pattern or therapeutic regimen.<br />

Revision as of 15:44, 15 July 2012

PepdEx: Smart Peptide-Based Therapies

  • Microbial biotechnology has applications in a wide spectrum of areas, from agriculture, environmental protection to biofuels. The original scheme is simple, for instance manipulate microbes to produce certain chemicals. As a medical-based team, we aim to design microbes to target human diseases. The ultimate goal is to use microbes as a general platform to do complex calculations that respond to conditions in human body, and then administer smart peptide-based therapies.
  • We will first use anti-obesity as a proof-of-principle application to this approach. Non-pathogenic E. Coli will live in the intestines and serve as a device to sense the presence of fatty acids, and as an output secret synthetic GLP-1 peptide to suppress the appetite. Appropriate signal peptide and Penetratin will be used to facilitate peptide secretion and intestinal uptake, respectively. Since the intestine is a highly fluctuating environment, we will incorporate a two-filter circuit with anti-noise function, so that the system only responds to sustained stimulus. In addition, due to burden effect bacteria with artificial plasmids will be gradually lost from the population without selection pressure; plasmid segregational instability will also introduce undesirable alterations to the final function for systems encoded in multiple plasmids (as in our case).
  • To circumvent this, we also incorporate plasmid stabilization modules including partition system and multimer resolution system. With this general concept we will also explore other pieces of human disease with alternative circuit designs, for instance with an oscillator circuit we can periodically deliver synthetic peptides based on natural secretory pattern or therapeutic regimen.
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