Generator

Part:BBa_K1598003

Designed by: Marta Napiorkowska   Group: iGEM15_UCL   (2015-08-27)

RBS-ChAT-6xHis-Terminator
This part consists of B0034 RBS, human choline acetyltransferase (ChAT) gene with C-terminal His tag, and B0015 terminator.

Usage and Biology

Choline acetyltransferase (ChAT) catalyses synthesis of acetylcholine from choline and acetyl-CoA. Acetylcholine is a versatile neurotransmitter that has mediates signalling in central nervous system and brain as well as peripheral nervous system. Acetylcholine has been implicated in cognition, memory, and learning functions [1]. Acetylcholine is also a principal neurotransmitter in vagal nerve, which connects brain to digestive system [2]. Acetylcholine released at the efferent vagus nerve endings decreases the excessive production of inflammatory cytokines such as IL-1, IL-6 and tumor necrosis factor-α (TNF-α) [3]. These inflammatory cytokines are elevated in patients with major depression [4] and have been shown to induce depressive-like behaviour in mice [5] and humans [6].

In humans, ChAT expression requires microbiota-dependent signalling and does not begin until microbial gut colonization after birth. [7]. Hence, imbalances in gut microflora can lead to disrupted acetylcholine activity, which has been strongly linked to depression. We propose to explore the acetylcholine-producing probiotics as a solution for restoring the proper functioning of cholinergic system in patients with depression and other psychiatric diseases.


Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    INCOMPATIBLE WITH RFC[12]
    Illegal NheI site found at 682
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal XhoI site found at 303
    Illegal XhoI site found at 1770
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    INCOMPATIBLE WITH RFC[25]
    Illegal NgoMIV site found at 1095
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal BsaI.rc site found at 1765


References

[1] Klinkenberg, I., Sambeth, A. and Blokland, A. Acetylcholine and attention. Behavioural Brain Research, 2011, 221(2), pp.430-442.
[2] Lleó, A., Greenberg, S. and Growdon, J. Current Pharmacotherapy for Alzheimer's Disease. Annual Review of Medicine, 2006, 57(1), pp.513-533
[3]
[4] Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. and Lanctôt, K. (2010). A Meta-Analysis of Cytokines in Major Depression. Biological Psychiatry, 67(5), pp.446-457.
[5] Larson, S. and Dunn, A. Behavioral Effects of Cytokines. Brain, Behavior, and Immunity, 2001, 15(4), pp.371-387
[6] Capuron, L., Ravaud, A., Neveu, P., Miller, A., Maes, M. and Dantzer, R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Molecular Psychiatry, 2002, 7(5), pp.468-473
[7] Reardon, C., Duncan, G., Brustle, A., Brenner, D., Tusche, M., Olofsson, P., Rosas-Ballina, M., Tracey, K. and Mak, T. Lymphocyte-derived ACh regulates local innate but not adaptive immunity. Proceedings of the National Academy of Sciences, 2013, 110(4), pp.1410-1415.

[edit]
Categories
Parameters
None