User:Cecilia Cisar/Notebook/Mod 3 Research Proposal

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* Some bacteria use miRNA to target and post-transcriptionally repress proteins that are involved in innate immune response, [2] and other bacteria release effectors that inhibit miRNA immune response. [3] (Conversely, some miRNA-regulated immune response pathways are activated by bacteria. [4])
* Some bacteria use miRNA to target and post-transcriptionally repress proteins that are involved in innate immune response, [2] and other bacteria release effectors that inhibit miRNA immune response. [3] (Conversely, some miRNA-regulated immune response pathways are activated by bacteria. [4])
-
* Bacteria could be designed to treat various kinds of tumors based on their miRNA expression fingerprint by up/down regulating miRNA expression.
+
* Bacteria could be designed to treat various kinds of tumors based on their miRNA expression fingerprint through up/down regulation of oncogene miRNA expression.
 +
 
 +
==Potential Problems==
 +
*Immune response
 +
**Cancer patients may already be immunocompromised through other treatments, so this may not be as big of an issue as it would initially seem, but this leads to...
 +
*Pathogenicity
 +
**If my 20.020 project taught me anything, it's that people are squeamish about introducing bacteria into things even if there isn't anything to point towards it being problematic.
 +
**Would saying that there ''should'' be nothing wrong with the chassis and that it'll have to go through clinical testing be enough?
 +
*Targeting
 +
**It seems that my earlier reading of the interferon-gamma paper was incorrect, and that bacteria do not specifically target things based on miRNA signatures...
 +
**Could we rely on bacteria to stay localized, depending on treatment method?
 +
**Would regulation of oncogenes in non-target area be an issue? I want to think it would just make cancer-causing mutations even ''less'' likely in affected areas...
==References==
==References==

Revision as of 04:06, 6 May 2014

Contents

Project Description

Overview

  • MiRNAs are believed to be important in oncogenesis, as different groups of miRNAs act as either tumor suppressors or oncogenes. Changes in miRNA expression have been detected in many types of human cancers, in a way that seems to be linked to genomic amplifications, mutations, and deletions. "MiRNA expression fingerprints correlate with clinical and biological characteristics of tumours, including tissue type, differentiation, aggression and response to therapy." [1]
  • Some bacteria use miRNA to target and post-transcriptionally repress proteins that are involved in innate immune response, [2] and other bacteria release effectors that inhibit miRNA immune response. [3] (Conversely, some miRNA-regulated immune response pathways are activated by bacteria. [4])
  • Bacteria could be designed to treat various kinds of tumors based on their miRNA expression fingerprint through up/down regulation of oncogene miRNA expression.

Potential Problems

  • Immune response
    • Cancer patients may already be immunocompromised through other treatments, so this may not be as big of an issue as it would initially seem, but this leads to...
  • Pathogenicity
    • If my 20.020 project taught me anything, it's that people are squeamish about introducing bacteria into things even if there isn't anything to point towards it being problematic.
    • Would saying that there should be nothing wrong with the chassis and that it'll have to go through clinical testing be enough?
  • Targeting
    • It seems that my earlier reading of the interferon-gamma paper was incorrect, and that bacteria do not specifically target things based on miRNA signatures...
    • Could we rely on bacteria to stay localized, depending on treatment method?
    • Would regulation of oncogenes in non-target area be an issue? I want to think it would just make cancer-causing mutations even less likely in affected areas...

References

  1. Calin, George A., and Carlo M. Croce. "MicroRNA signatures in human cancers." Nature Reviews Cancer 6.11 (2006): 857-866.
  2. Ma, Feng, et al. "The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ."Nature immunology 12.9 (2011): 861-869.
  3. Navarro, Lionel, et al. "Suppression of the microRNA pathway by bacterial effector proteins." Science 321.5891 (2008): 964-967.
  4. Taganov, Konstantin D., et al. "NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses." Proceedings of the National Academy of Sciences 103.33 (2006): 12481-12486.

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