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Team:HUST-China
From 2013.igem.org
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The morning peak is also called “death | The morning peak is also called “death | ||
time”,for it’s unlikely to take drugs before waking. Propionate, a short chain fatty acid, | time”,for it’s unlikely to take drugs before waking. Propionate, a short chain fatty acid, | ||
| - | was recently shown to produce an acute hypotensive response.2013 HUST-China iGEM use a synthetic way to combine bio-oscillator with propionate-producing | + | was recently shown to produce an acute hypotensive response.2013 HUST-China iGEM use a synthetic way to combine bio-oscillator with propionate-producing enzyme |
| - | + | gene, trying to build a gut probiotic which can release propionate | |
| - | + | periodically in accord with the rhythm of human BP. This could be a great substitute for chemical drugs by saving patients from drug dependence and the risk of sudden death at | |
| - | + | morning BP peak time. | |
</div> | </div> | ||
<div class="clearfix"></div> | <div class="clearfix"></div> | ||
Revision as of 00:43, 28 September 2013
Abstract
Hypertension has become the leading risk factor for mortality worldwide. Human’s blood pressure (BP) has a basic daily rhythm with two
peaks,6:00 to 10:00 in the
morning and 16:00 to18:00 in the afternoon.
The morning peak is also called “death
time”,for it’s unlikely to take drugs before waking. Propionate, a short chain fatty acid,
was recently shown to produce an acute hypotensive response.2013 HUST-China iGEM use a synthetic way to combine bio-oscillator with propionate-producing enzyme
gene, trying to build a gut probiotic which can release propionate
periodically in accord with the rhythm of human BP. This could be a great substitute for chemical drugs by saving patients from drug dependence and the risk of sudden death at
morning BP peak time.
The key part of the oscillator is araBAD/ lacZYA hybrid p-
romoter. It is activated by the AraC protein in the prese-
nce of arabinose and repressed by the LacI protein in the absence of IPTG, constructing two feedback loops with opposite effects.And the differential activity of the two feedback loops can drive oscillatory behaviour.
A four-gene operon in E.coli K12 genome which includes sbm,ygfG,ygfH and ygfD, is significant in the metabolic pathway that converts succinate to propionate through Wood-Werkman reaction. We constructed effective expression plasmid to increase the quantity of the four enzymes independently. By measuring the propionate amount, we figured out which of the four is the most effective.
In the future, we will use the gene of key enzyme of propionate producing reaction to replace mRFP in the oscillator as output. And we hope to see periodical
release of propionate in accord with the rhythm of human BP.
Our project is divided into three parts: the construction of the biological oscillator, the output evaluation of propionate by HPLC and the standardization of four genes.
Detailed analysis of the oscillator makes us clearer about how it works. From the establishment of DDEs (Delayed Differential Equations) to parameter sweep and sensitivity analysis, we know how each parameter contributes to the period. The MCOS (Multi Cells Oscillation Simulation) shows us the feasibility of a group of oscillators that can be eventually applied in practice in vivo (colon).
Human practice:We have done a remarkable job in intro-
ducing high school students synthetic biology and
iGEM jamborees as well as motivating them towards fu-
ture participation in the iGEM. Besides, we collaborated with two other iGEM teams by sharing plasmids and characterizing their parts. Furthermore, we made a public speech in our school about what we achieved,sha-
ring the feelings in the iGEM competition.
Acknowledgement
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Powered by the iGEM team comes from HuaZhong University of Science and Techology
HUST-China
