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{{Virginia}}
 
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<img src="https://stemedhub.org/groups/aau_virginia/Image:institution_logo.png"></img>
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<p>iGEM 2015</p>
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<p>Welcome the University of Virginia iGEM 2015 Wiki! Use the navigation bar at the top of every page to move between pages. Please let us know if you have any comments or questions about our project by visiting the “Contact Us” page.</p>
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<p>(click to close)</p>
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<h2>
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House of Carbs
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<p>A Novel Solution to Minimizing Postprandial Hyperglycemic Spikes</p>
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</h2>
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</div>
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<div id="description-wrapper">
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<div id="description-text-wrapper">
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<h1>Project Overview</h1>
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<h3 id="h3-1">The Problem: Diabetes Mellitus and Hyperglycemia</h3>
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<p>From diabetes mellitus a number of devastating complications, such as amputations, blindness, crippling neuropathies, and many others, can arise from increased blood sugar levels on a regular basis, but many of
 +
the major complications of diabetes arise from drastic fluctuations in the blood glucose
 +
level (Ceriello et al., 2012). Up to two-thirds of people with diabetes die of
 +
cardiovascular disease (CVD) brought about by diabetes-related macrovascular diseases
 +
(Deshpande et al. 2008). In fact, the risk for cardiovascular disease mortality is 2 to 4
 +
times higher in people with diabetes than in people who do not have diabetes.
 +
Additionally, diabetic retinopathy is the most common microvascular complication
 +
among people with diabetes and results in more than 10,000 new cases of blindness per
 +
year. Retinopathy is associated with prolonged hyperglycemia; it is slow to develop, and
 +
there is some evidence that it can begin to develop as early as 7 years before clinical
 +
diagnosis of diabetes (Deshpande et al., 2008).
 +
</p>
 +
<p>Postprandial (post-meal) blood sugar spikes specifically are one of the most
 +
damaging complications of diabetes (Parkin et al., 2002). Many diabetics are able to
 +
effectively manage post-meal glycemic spikes with self-administered doses of insulin,
 +
but these hyperglycemic incidents still kill more Americans per year than any other
 +
diabetes-related complications (Parkin et al., 2002). Arguably, the gravest consequence of
 +
glycemic spikes in diabetes patients is the development of progressive macrovascular
 +
disease (MVD), which affects the large blood vessels of the body, hardening and
 +
blocking these vessels (Ceriello et al., 2012). MVD is the leading cause of death among
 +
T2DM patients in the United States, causing up to 65% of diabetes-related deaths, making it a huge target for diabetes treatments research (Deshpande et al., 2008). MVD
 +
also frequently leads to other severe complications such as ischemia in the extremities
 +
and blindness (Haffner et al., 1998).
 +
</p></div>
 +
<h3 id="h3-2">Controlling Hyperglycemic Spikes</h3><div id="des2">
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<p>For many T1DM and T2DM patients, it has been shown that the regular
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    {{Virginia}} <!-- Bootstrap import == Latest compiled and minified CSS -->
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control and management of blood glucose levels prevents many of the vascular
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complications of the disease, but most of the time control over glucose is difficult to
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attain because the self-dosing insulin treatment system that a lot of moderately to
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severely sick diabetes patients use is often hard to calibrate and use (Parkin et al., 2002).
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</p>
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<p>Compared to sucrose-rich food, starch-rich food has been found to create less
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        <h1>Welcome to the University of Virginia iGEM 2015 Wiki</h1>
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fluctuation in blood glucose levels, and thus is beneficial to diabetes patients and
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+
hyperglycemia patients. There is evidence that this flatter response caused by a starch
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+
rich meal is associated with the slower rate of digestion of complex sugars versus simple
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        <p>Use the navigation bar at the top of every page to move between
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sugars (Jenkins, Wolever, & Jenkins, 1988). Thus, if some of the simple sugars are first
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        pages. Please let us know if you have any comments or questions about
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converted into complex saccharides inside the E. coli and then released back into small
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        our project by visiting the “Contact Us” page.</p>
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intestine, a similar flatter glycemic response will take place, which will be beneficial to
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<h3 id="h3-3">Our Devices</h3><div id="des3">
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                        <a href="/Team:Virginia">Home</a>
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<p style="margin-bottom:30px;"> We have assembled one plasmid with genes that dictate a controllable level of simple sugars uptake and one plasmid to produce glucan and fructan from simple sugars and then lyse to release the complex sugars back into the environment. In essence, this microbial device runs on two genetic devices -- an uptake circuit and a polymerization circuit. </p></div>
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<p style="font-style:italic; border-top:1px dotted #007bb6"> In order to learn more details, please visit the <a href="/Team:Virginia/Project">Project page.</a> </p>
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<div id="ref-content">
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<h3>References</h3>
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<p>A. Ceriello, S. Colagiuri, (2011). Guideline for management of postmeal glucose in
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                    <li>
+
diabetes. International Diabetes Federation Guideline Development Group,
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                        <a href="/Team:Virginia/Project">Project</a>
+
http://www.idf.org/sites/default/files/postmeal%20glucose%20guidelines.pdf ,
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                    </li>
+
Accessed May. 6th, 2015
−
 
+
</p>
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<p>American Diabetes Association (2014). National Diabetes Statistics Report.
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                    <li>
+
http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf
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                        <a href="/Team:Virginia/Practices">Policy and
+
Accessed May. 5th, 2015
−
                        Practices</a>
+
</p>
−
                    </li>
+
<p>Anal, A. K., & Singh, H. (2007). Recent advances in microencapsulation of probiotics for
−
 
+
industrial applications and targeted delivery. Trends in Food Science &
−
 
+
Technology, 18(5), 240–251. http://doi.org/10.1016/j.tifs.2007.01.004
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                    <li>
+
</p>
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                        <a href="/Team:Virginia/Attributions">Attributions</a>
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<p>Anan, F., Masaki, T., Eto, T., Fukunaga, N., Iwao, T., Kaneda, K., ... Yoshimatsu, H.
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                    </li>
+
(2008). Postchallenge Plasma Glucose and Glycemic Spikes Are Associated with
−
 
+
Pulse Pressure in Patients with Impaired Glucose Tolerance and Essential
−
 
+
Hypertension. Hypertension Research, 31(8), 1565–1571.
−
                    <li>
+
http://doi.org/10.1291/hypres.31.1565
−
                        <a href="/Team:Virginia/Contact_us">Contact Us</a>
+
</p>
−
                    </li>
+
<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
−
                </ul>
+
of Health-System Pharmacists, Inc.; ©2008. Acarbose; [revised 2015 Feb. 15;
−
            </div>
+
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
−
        </div>
+
http://www.nlm.nih.gov/medlineplus/druginfo/meds/ a696015.html
−
 
+
</p>
−
 
+
<p>AHFS Consumer Medication Information [Internet]. Bethesda (MD): American Society
−
        <div class="jumbotron">
+
of Health-System Pharmacists, Inc.; ©2008. Pramlintide; [revised 2015 Feb. 15;
−
            <h2>House of Carbs</h2>
+
reviewed 2015 Apr. 28; cited 2015 May. 3]; Available from:
−
 
+
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a605031.html
−
 
+
</p>
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            <p>A Novel Solution to Minimizing Postprandial Hyperglycemic
+
<p>Banguela, A., Arrieta, J. G., Rodríguez, R., Trujillo, L. E., Menéndez, C., & Hernández,
−
            Spikes</p>
+
L. (2011). High levan accumulation in transgenic tobacco plants expressing the
−
        </div>
+
Gluconacetobacter diazotrophicus levansucrase gene. Journal of Biotechnology,
−
 
+
154(1), 93–98. http://doi.org/10.1016/j.jbiotec.2011.04.007
−
 
+
</p>
−
        <div id="description-wrapper">
+
<p>Barr EL, Zimmet PZ, Welborn TA et al. (2007). "Risk of cardiovascular and all-cause
−
            <div id="description-text-wrapper">
+
mortality in individuals with diabetes mellitus, impaired fasting glucose, and
−
                <h1>Project Overview</h1>
+
impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study
−
 
+
(AusDiab)". Circulation 116 (2): 151–7.
−
 
+
</p>
−
                <p>From diabetes mellitus a number of devastating
+
<p>Bernard, A. M., Anderson, L., Cook, C. B., & Phillips, L. S. (1999). What do internal
−
                complications, such as amputations, blindness, crippling
+
medicine residents need to enhance their diabetes care? Diabetes Care, 22(5),
−
                neuropathies, and many others, can arise from increased blood
+
661–666. http://doi.org/10.2337/diacare.22.5.661
−
                sugar levels on a regular basis, but many of the major
+
</p>
−
                complications of diabetes arise from drastic fluctuations in
+
<p>Boada C, Martínez-Moreno J. Pathophysiology of diabetes mellitus type 2: beyond the
−
                the blood glucose level (Ceriello et al., 2012). Up to
+
duo "insulin resistance-secretion deficit.". Nutricion Hospitalaria [serial online].
−
                two-thirds of people with diabetes die of cardiovascular
+
March 2, 2013;28:78-87. Available from: Fuente Académica, Ipswich, MA.
−
                disease (CVD) brought about by diabetes-related macrovascular
+
Accessed April 16, 2015.
−
                diseases (Deshpande et al. 2008). In fact, the risk for
+
</p>
−
                cardiovascular disease mortality is 2 to 4 times higher in
+
<p>B. Göke, H. F. (1995). Voglibose (AO128) Is an Efficient α-Glucosidase Inhibitor and  
−
                people with diabetes than in people who do not have diabetes.
+
Mobilizes the Endogenous GLP-1 Reserve. Digestion, 56(6), 493–501.
−
                Additionally, diabetic retinopathy is the most common
+
http://doi.org/10.1159/000201282
−
                microvascular complication among people with diabetes and
+
</p>
−
                results in more than 10,000 new cases of blindness per year.
+
<p>Brown, J. B., Harris, S. B., Webster-Bogaert, S., Wetmore, S., Faulds, C., & Stewart, M.
−
                Retinopathy is associated with prolonged hyperglycemia; it is
+
(2002). The role of patient, physician and systemic factors in the management of
−
                slow to develop, and there is some evidence that it can begin
+
type 2 diabetes mellitus. Family Practice, 19(4), 344–349.
−
                to develop as early as 7 years before clinical diagnosis of
+
http://doi.org/10.1093/fampra/19.4.344
−
                diabetes (Deshpande et al., 2008).</p>
+
</p>
−
 
+
<p>Butterworth, P. J., Warren, F. J., & Ellis, P. R. (2011). Human α-amylase and starch
−
 
+
digestion: An interesting marriage. Starch - Stärke, 63(7), 395–405.
−
                <p>Postprandial (post-meal) blood sugar spikes specifically are
+
http://doi.org/10.1002/star.201000150
−
                one of the most damaging complications of diabetes (Parkin et
+
</p>
−
                al., 2002). Many diabetics are able to effectively manage
+
<p>Centers for Disease Control and Prevention. (2014). National Diabetes Statistics Report.</p>
−
                post-meal glycemic spikes with self-administered doses of
+
<p>Chiasson, J.-L., Josse, R. G., Gomis, R., Hanefeld, M., Karasik, A., & Laakso, M. (2002).
−
                insulin, but these hyperglycemic incidents still kill more
+
Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM
−
                Americans per year than any other diabetes-related
+
randomised trial. The Lancet, 359(9323), 2072–2077.
−
                complications (Parkin et al., 2002). Arguably, the gravest
+
http://doi.org/10.1016/S0140-6736(02)08905-5
−
                consequence of glycemic spikes in diabetes patients is the
+
</p>
−
                development of progressive macrovascular disease (MVD), which
+
<p>Chiasson, J.-L., Josse, R. G., Hunt, J. A., Palmason, C., Rodger, N. W., Ross, S. A., ...
−
                affects the large blood vessels of the body, hardening and
+
Wolever*, T. M. S. (1994). The Efficacy of Acarbose in the Treatment of Patients
−
                blocking these vessels (Ceriello et al., 2012). MVD is the
+
with Non–Insulin-Dependent Diabetes Mellitus: A Multicenter, Controlled
−
                leading cause of death among T2DM patients in the United
+
Clinical Trial. Annals of Internal Medicine, 121(12), 928–935.
−
                States, causing up to 65% of diabetes-related deaths, making it
+
http://doi.org/10.7326/0003-4819-121-12-199412150-00004
−
                a huge target for diabetes treatments research (Deshpande et
+
Crude and Age-Adjusted Rate per 100 of Civilian, Noninstitutionalized Population with
−
                al., 2008). MVD also frequently leads to other severe
+
Diagnosed Diabetes, United States, 1980–2011. (2014, September 5). Retrieved
−
                complications such as ischemia in the extremities and blindness
+
April 24, 2015, from
−
                (Haffner et al., 1998).</p>
+
http://www.cdc.gov/diabetes/statistics/prev/national/figage.htm
−
 
+
</p>
−
 
+
<p>Dedonder, R. 1966. Levansucrase from Bacillus subtilis. Methods Enzymol. 8:500–505.</p>
−
                <p>For many T1DM and T2DM patients, it has been shown that the
+
<p>Deshpande, A. D., Harris-Hayes, M., & Schootman, M. (2008). Epidemiology of diabetes
−
                regular control and management of blood glucose levels prevents
+
and diabetes-related complications. Physical therapy, 88(11), 1254-1264.
−
                many of the vascular complications of the disease, but most of
+
</p>
−
                the time control over glucose is difficult to attain because
+
<p>D.M. Nathan, P.A. Cleary, J.Y. Backlund, S.M. Genuth, J.M. Lachin, T.J. Orchard, et al.,
−
                the self-dosing insulin treatment system that a lot of
+
Intensive diabetes treatment and cardiovascular disease in patients with type 1
−
                moderately to severely sick diabetes patients use is often hard
+
diabetes, N Engl J Med, 353 (2005), pp. 2643–2653
−
                to calibrate and use (Parkin et al., 2002).</p>
+
</p>
−
 
+
<p>D.R. Whiting, L. Guariguata, C. Weil, J. Shaw, IDF diabetes atlas: global estimates of the
−
 
+
prevalence of diabetes for 2011 and 2030 Diabetes Res Clin Pract, 94 (2011), pp.
−
                <p>Compared to sucrose-rich food, starch-rich food has been
+
311–321
−
                found to create less fluctuation in blood glucose levels, and
+
</p>
−
                thus is beneficial to diabetes patients and hyperglycemia
+
<p>Duncan, A. E. (2012). Hyperglycemia and Perioperative Glucose Management.Current
−
                patients. There is evidence that this flatter response caused
+
Pharmaceutical Design, 18(38), 6195–6203.
−
                by a starch rich meal is associated with the slower rate of
+
</p>
−
                digestion of complex sugars versus simple sugars (Jenkins,
+
<p>Edelman, P. S., Maier, H., & Wilhelm, K. (2012). Pramlintide in the Treatment of
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                Wolever, & Jenkins, 1988). Thus, if some of the simple sugars
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Diabetes Mellitus. BioDrugs, 22(6), 375–386. http://doi.org/10.2165/0063030-
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                are first converted into complex saccharides inside the E. coli
+
200822060-00004
−
                and then released back into small intestine, a similar flatter
+
</p>
−
                glycemic response will take place, which will be beneficial to
+
<p>Ferraris, R. P., Yasharpour, S. A. S. A. N., Lloyd, K. C., Mirzayan, R. A. F. F. Y., &
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                the patients.</p>
+
Diamond, J. M. (1990). Luminal glucose concentrations in the gut under normal
−
 
+
conditions. American Journal of Physiology-Gastrointestinal and Liver
−
 
+
Physiology, 259(5), G822-G837.
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                <p>We have assembled one plasmid with genes that dictate a
+
</p>
−
                controllable level of simple sugars uptake and one plasmid to
+
<p>Gay, P., Le Coq, D., Steinmetz, M., Ferrari, E., & Hoch, J. A. (1983). Cloning structural
−
                produce glucan and fructan from simple sugars and then lyse to
+
gene sacB, which codes for exoenzyme levansucrase of Bacillus subtilis:
−
                release the complex sugars back into the environment. In
+
expression of the gene in Escherichia coli. Journal of bacteriology,153(3), 1424-
−
                essence, this microbial device runs on two genetic devices --
+
1431.
−
                an uptake circuit and a polymeriztion circuit.</p>
+
</p>
−
 
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<p>Gray, G. M., & Ingelfinger, F. J. (1966). Intestinal absorption of sucrose in man:
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interrelation of hydrolysis and monosaccharide product absorption. Journal of
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                <p>In order to learn more details, please visit the “Project”
+
Clinical Investigation, 45(3), 388.
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                page.</p>
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</p>
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<p>Grant, R. W., Buse, J. B., & Meigs, J. B. (2005). Quality of Diabetes Care in U.S.
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Academic Medical Centers Low rates of medical regimen change. Diabetes Care,  
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28(2), 337–442. http://doi.org/10.2337/diacare.28.2.337
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<p>Grant, R. W., Pirraglia, P. A., Meigs, J. B., & Singer, D. E. (2004). Trends in complexity
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of diabetes care in the United States from 1991 to 2000. Archives of Internal
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<p>Halschou, K., Bukhave, K., & Rikardt, J. (2012). Intestinal Disaccharidase Activity and
−
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Uptake of Glucose from Sucrose. In S. Chackrewarthy (Ed.), Glucose Tolerance.
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InTech. Retrieved from http://www.intechopen.com/books/glucose-
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tolerance/intestinal-disaccharidase-activity-and-uptake-of-glucose-from-sucrose
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<p>Hanahan, D. (1983). Studies on transformation of Escherichia coli with plasmids. Journal
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of Molecular Biology, 166(4), 557–580.
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                    <p>PROJECT</p>
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<p>Hoffmann, J., & Spengler, M. (1997). Efficacy of 24-Week Monotherapy With Acarbose,  
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The American Journal of Medicine, 103(6), 483–490.
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http://doi.org/10.1016/S0002-9343(97)00252-0
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Intensive blood-glucose control with sulphonylureas or insulin compared with
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conventional treatment and risk of complications in patients with type 2 diabetes  
−
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<p>Jenkins, D. J. A., Wolever, T. M. S., & Jenkins, A. L. (1988). Starchy Foods and
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Glycemic Index. Diabetes Care, 11(2), 149–159.
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http://doi.org/10.2337/diacare.11.2.149
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Physician, 75(12), 1831–1835.
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<p>J Reizer, S. L. S. (1992). Functional interactions between proteins of the
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phosphoenolpyruvate:sugar phosphotransferase systems of Bacillus subtilis and  
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Escherichia coli. The Journal of Biological Chemistry, 267(13), 9158–69.
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Jenkins, D. J., Wolever, T. M., & Jenkins, A. L. (1988). Starchy foods and glycemic
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index. Diabetes care, 11(2), 149-159.
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<p>Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Cotran, Ramzi S. ; Robbins, Stanley L.
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(2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). Philadelphia,
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Pa.: Saunders. pp. 1194–1195. ISBN 0-7216-0187-1. Lancet. 1998 Sep 12;
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352(9131):837-53.
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<p>Kundig, W., Ghosh, S., & Roseman, S. (1964). PHOSPHATE BOUND TO HISTIDINE
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IN A PROTEIN AS AN INTERMEDIATE IN A NOVEL PHOSPHO-
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TRANSFERASE SYSTEM. Proceedings of the National Academy of Sciences of  
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the United States of America, 52, 1067–1074.
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</p>
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<p>Lebovitz, H. E. (1997). ALPHA-GLUCOSIDASE INHIBITORS. Endocrinology and
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Metabolism Clinics of North America, 26(3), 539–551.
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http://doi.org/10.1016/S0889-8529(05)70266-8
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Vakil, N. (2007). World Gastroenterology Organisation Practice Guidelines.
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Dysphagia. Retrieved from http://almacen-
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gpc.dynalias.org/publico/Dysphagia%20WGO%202004%20Ingles.pdf
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<p>Man, C. D., Camilleri, M., & Cobelli, C. (2006). A System Model of Oral Glucose
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<p>Meigs, J. B., Nathan, D. M., Wilson, P. W., Cupples, L. A., & Singer, D. E. (1998).
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Metabolic risk factors worsen continuously across the spectrum of nondiabetic
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            <p>Charlottesville, Virginia 22904</p>
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glucose tolerance. The Framingham Offspring Study. Annals of Internal Medicine,  
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128(7), 524–533.
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and salivary α-amylases on maltooligosaccharides: Evaluation of kinetic
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parameters. Clinica Chimica Acta, 97(2–3), 253–260.
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and Other Categories of Glucose Intolerance. Diabetes, 28(12), 1039–1057.  
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http://doi.org/10.2337/diab.28.12.1039
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<p>Nissle, A. (1959). [Explanations of the significance of colonic dysbacteria & the  
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adults. The Third National Health and Nutrition Examination Survey, 1988-1994.
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<p>Rathmann, W., & Giani, G. (2004). Global Prevalence of Diabetes: Estimates for the
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Year 2000 and Projections for 2030: Response to Wild et al. Diabetes Care, 2568-
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<p>Recorbet, G. H. I. S. L. A. I. N. E., Robert, C., Givaudan, A., Kudla, B., Normand, P., &
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Faurie, G. (1993). Conditional suicide system of Escherichia coli released into
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soil that uses the Bacillus subtilis sacB gene. Applied and environmental
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<p>Ried, J. L., and A. Collmer. 1987. An nptI-sacB-sacR cartridge for constructing directed,
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unmarked mutations in Gram-negative bacteria by marker exchange-eviction
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mutagenesis. Gene 57:239–246.
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Type 2 Diabetes Using Basal Insulin. Diabetes Care, 30(11), 2794–2799.  
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Nissle 1917 - Features of a Versatile Probiotic. Microbial Ecology in Health and  
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heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and
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Hanefeld, M. (2000). Postchallenge plasma glucose and glycemic spikes are more
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+
</div>
−
            font-weight: bold;
+
<div class="box" id="b6">
−
            padding: 14px 10px;
+
<a href="#">
−
            text-transform: uppercase;
+
<p>ABOUT</p>
−
            border-radius:5px;
+
</a>
−
            }
+
</div>
−
            .nav a:hover{
+
</div>
−
            color:#fff;
+
</div>
−
            background-color:#007bb6;
+
</div>
−
            text-decoration:none;
+
</div>
−
            }
+
<footer>
−
            .nav li {
+
<div id="foot-img">
−
            display: inline;
+
<img src="https://static.igem.org/mediawiki/2015/d/d1/Virginia_logo4.png"></img>
−
            font-family: Arial;
+
</div>
−
            }
+
<div id="foot-text">
−
            .nav .container {
+
<p>University of Virginia iGEM</p>
−
            padding-top:5px;
+
<p>148 Gilmer Hall</p>
−
            padding-bottom:5px;
+
<p>485 McCormick Road</p>
−
            }
+
<p>Charlottesville, Virginia 22904</p>
−
            .row {
+
<p>United States of America</p>
−
            width:100%;
+
<p></p>
−
            }
+
<p><a href="mailto:virginia.igem@gmail.com">
−
            #content h1.firstHeading {
+
virginia.igem@gmail.com</a>
−
            visibility:hidden;
+
</p>
−
            }
+
</div>
−
            #content {
+
</footer>
−
            margin: 0px 0px 0px 0px;
+
</div>
−
            padding:0px 0px 0px 0px;
+
<style type="text/css">
−
            width:100%;
+
#description-wrapper {
−
            height:auto;
+
width:100%;
−
            background-color: rgb(0,0,0);
+
height:auto;
−
            }
+
padding: 50px;
−
            html {
+
padding-bottom:150px;
−
            background-color:#191919;
+
background:#000000;
−
            color: #fff
+
border-bottom: 3px dotted #fff;
−
            font-family: Century Gothic, sans-serif;
+
}
−
            }
+
#description-text-wrapper {
−
            #top_menu_14 {
+
width:85%;
−
            /*BORDER ATTRIBUTES*/
+
margin-left:7.5%;
−
            border-top:5px solid #007bb6;
+
height:auto;
−
            background-color: #003F87;
+
}
−
            border-color:#003F87;
+
#description-wrapper p {
−
            }
+
font-size: 18px;
−
            #top_menu_14 li.has_submenu:hover {
+
font-family:Arial;
−
            opacity:1.0;
+
color:#fff;
−
            background-color:#007bb6;
+
}
−
            text-decoration:none;
+
#description-wrapper h1 {
−
            }
+
font-size: 36px;
−
            #top_menu_14 li:hover {
+
font-family:Arial;
−
            opacity:1.0;
+
color:#fff;
−
            background-color:#007bb6;
+
text-align:center;
−
            text-decoration:none;
+
font-weight:bold;
−
            }
+
}
−
            footer {
+
footer div img {
−
            width:100%
+
width:auto;
−
            height:300px;
+
height:200px;
−
            padding:25px 25px 25px 25px;
+
}
−
            background:#000000;
+
footer div {
−
            clear:both;
+
overflow:hidden;
−
            }
+
display:inline-block;
−
            footer p:first-child {
+
float:none;
−
            font-weight:bold;
+
}
−
            font-family:Arial;
+
footer div:first-child {  
−
            font-size:18px;
+
float:right;
−
            text-decoration:underline;
+
top:10px;
−
            }
+
height:90%;
−
            footer a {
+
width:25%
−
            color:#fff;
+
margin: 1%;
−
            }
+
display:inline;
−
            footer p {
+
overflow:hidden;
−
            width:auto;
+
}
−
            }
+
.jumbotron {
−
            p {  
+
height: auto;
−
            color:white;
+
background-size: 100%;
−
            font-family: serif;
+
background-image: url("https://static.igem.org/mediawiki/2015/b/b8/Virginia_cells.jpg");
−
            float:center;
+
padding:60px;
−
            clear:both;
+
margin:0px 0px 0px 0px;
−
            }
+
color:white;
−
            #bolded {
+
opacity:0.9;
−
            font-weight:bold;
+
}
−
            }
+
.jumbotron h2 {
−
            #above-nav{
+
text-align:center;
−
            margin-bottom:10px;
+
color:#ffffff;
−
            float:left;
+
font-size:70px;
−
            font-size:30px;
+
font-weight:bold;
−
            text-align:center;
+
padding-bottom:30px;
−
            font-family:Helvetica;
+
margin-bottom:0px;
−
            text-transform:uppercase;
+
width:50%;
−
            text-shadow: 2px 2px #007bb6;
+
opacity:1;
−
            padding-left:25%;
+
margin-left:25%;
−
            }
+
background-color:#007bb6;
−
            #top-part a {
+
border-radius:30px;
−
            width:auto;
+
text-shadow:2px 2px 2px black;
−
            height:auto;
+
box-shadow: 5px 5px 10px #191919;
−
            margin-right:20px;
+
}
−
            }
+
.jumbotron h1 {
−
            #facebook{
+
color: #fff;
−
            height:30px;
+
opacity:1;
−
            width:30px;
+
font-size: 48px;   
−
            }
+
font-weight: bold;
−
            #twitter{
+
text-align:center;
−
            height:40px;
+
padding-bottom:20px;
−
            width:40px;
+
}
−
            }
+
.learn-more {
−
            #facebook:hover{
+
width:100%;
−
            opacity:0.5;
+
background-color:#000000;
−
            }
+
text-align:center;
−
            #twitter:hover{
+
}
−
            opacity:0.5;
+
.learn-more .container .row {
−
            }
+
padding-bottom: 20px;
−
            #icon-box{
+
padding-top:30px;
−
            display:inline;
+
}
−
            float:right;
+
.learn-more h3 {
−
            }
+
font-family: 'Shift', sans-serif;
−
            #top-part{
+
font-size: 18px;
−
            display:inline;
+
font-weight: bold;
−
            height:56px;
+
text-align:center;
−
            position:fixed;
+
}
−
            top:14px;
+
.learn-more a {
−
            float:center;
+
color:#007bb6;
−
            background:#003F87;
+
}
−
            width:100%;
+
.learn-more img {
−
            z-index:10;
+
width: 90%;
−
            font-weight:bold;
+
height: auto;
−
            padding-top:15px;
+
border-radius:20%;  
−
            }
+
box-shadow: 5px 5px 2px #888888;
−
    .box{
+
}
−
            width:60%;
+
.nav {
−
            height:100px;
+
background-color: #003F87;
−
            display:inline-block;
+
width:100%;
−
            margin-left:20%;
+
float:top;   
−
            margin-top:25px;
+
position:fixed;
−
            margin-bottom:10px;
+
top:70px;
−
            border-radius:30px;
+
z-index:10;
−
            border: 5px solid #007bb6;
+
//opacity:0.85;
−
            overflow:hidden;
+
border-bottom:5px;
−
            background-color:#003F87;
+
border-top:0px;
−
            float:left;
+
border-left:0px;
−
            }
+
border-right:0px;
−
            .box:hover{
+
border-color:#007bb6;
−
            box-shadow: 5px 5px 10px #555555;
+
border-style:solid;
−
            }
+
}
−
            .box img {
+
.nav a {
−
            margin:50px;  
+
color: rgb(256, 256, 256);
−
            width:70%;
+
font-size: 16px;
−
            height:auto;
+
font-weight: bold;
−
            margin-left:15%;
+
padding: 14px 10px;
−
            display:none;
+
text-transform: uppercase;
−
            border-radius:10px;
+
border-radius:5px;
−
            box-shadow:none;
+
}
−
            drop-shadow:none;
+
.nav a:hover{
−
            }
+
color:#fff;
−
            .box p {
+
background-color:#007bb6;
−
            font-family:Arial;
+
text-decoration:none;
−
            font-size:30px;
+
}
−
            font-weight:bold;
+
.nav li {
−
            padding-top:25px;
+
display: inline;
−
            text-align:center;
+
font-family: Arial;
−
            }
+
}
−
            .popup {
+
.nav .container {
−
            background:#000000;
+
padding-top:5px;
−
            width:60%;
+
padding-bottom:5px;
−
            position:fixed;
+
}
−
            top:200px;
+
.row {
−
            margin-left:20%;
+
width:100%;
−
            height:auto;
+
}
−
            border-radius:15px;
+
#content h1.firstHeading {
−
            border:5px solid #007bb6;
+
visibility:hidden;
−
            box-shadow: 5px 5px 10px #191919;
+
}
−
            }
+
#content {
−
            .popup h1 {
+
margin: 0px 0px 0px 0px;
−
            font-size:50px;
+
padding:0px 0px 0px 0px;
−
            font-weight:bold;
+
width:100%;
−
            width:90%;
+
height:auto;
−
            margin-left:5%;
+
background-color: rgb(0,0,0);
−
            text-align:center;
+
}
−
            font-family:Arial;
+
html {
−
            color:#fff;
+
background-color:#191919;
−
            padding:30px;
+
color: #fff
−
            background:#F59A2C;
+
font-family: Century Gothic, sans-serif;
−
            text-shadow: 2px 2px 4px #000000;
+
}
−
            border: none;
+
footer {
−
            border-radius:20px;
+
width:100%
−
            }
+
height:300px;
−
            .popup p{
+
padding:25px 25px 25px 25px;
−
            font-size:17px;
+
background:#000000;
−
            color:#fff;
+
clear:both;
−
            padding:10px;
+
}
−
            text-align:center;
+
footer p:first-child {
−
            font-family:Arial;
+
font-weight:bold;
−
            }
+
font-family:Arial;
−
            .popup p:last-child {
+
font-size:18px;
−
            font-size:10px;
+
text-decoration:underline;
−
            color:#fff;
+
}
−
            width:80%;
+
footer a {
−
            margin-left:10%;
+
color:#fff;
−
            height:auto;
+
}
−
            text-align:center;
+
footer p {
−
            }
+
width:auto;
−
            .jumbotron p {
+
}
−
            font-family:Arial;
+
p {  
−
            font-size:26px;
+
color:white;
−
            padding:5%;
+
font-family: serif;
−
            }
+
float:center;
−
 
+
clear:both;
−
 
+
}
−
    </style><script type="text/javascript">
+
#bolded {
−
        jQuery(document).ready(function(){
+
font-weight:bold;
−
                $(".popup").css("z-index","11");
+
}
−
                $(".back").css("opacity",".3");
+
#above-nav{
−
                //$("#top_menu_14").css("opacity",".3");
+
margin-bottom:10px;
−
                $(".popup").css("opacity","1");
+
float:left;
−
                $(".popup").click(function(){
+
z-index:15;
−
                    $(".popup").fadeOut("slow");
+
font-size:32px;
−
    $("*").css("opacity","1");
+
text-align:center;
−
    });
+
font-family:Century Gothic, sans-serif;
−
                $(".box").mouseenter(function(){
+
text-shadow: 2px 2px #007bb6;
−
                    $(this).css("width","80%");
+
padding-left:30%;
−
                    $(this).css("margin-left","10%");
+
padding-bottom:5px;
−
                    $("img", this).css("display","block");
+
}
−
                    $(this).css("height","auto");              
+
#top-part a {
−
    });
+
width:auto;
−
    $(".box").mouseleave(function(){
+
height:auto;
−
                    $(this).css("width","60%");
+
margin-right:20px;
−
                    $(this).css("margin-left","20%");
+
}
−
                    $(this).css("height","100px");
+
#facebook{
−
                    $("img", this).css("display","none");
+
height:30px;
−
                   
+
width:30px;
−
    });
+
}
−
    });
+
#twitter{
−
    </script>
+
height:40px;
−
</body>
+
width:40px;
 +
}
 +
#facebook:hover{
 +
opacity:0.5;
 +
}
 +
#twitter:hover{
 +
opacity:0.5;
 +
}
 +
#icon-box{
 +
display:inline;
 +
float:right;
 +
}
 +
#top-part{
 +
display:inline;
 +
height:56px;
 +
position:fixed;
 +
top:14px;
 +
float:center;
 +
background:#003F87;
 +
width:100%;
 +
z-index:10;
 +
font-weight:bold;
 +
padding-top:15px;
 +
}
 +
.box{
 +
width:60%;
 +
height:100px;
 +
display:inline-block;
 +
margin-left:20%;
 +
margin-top:25px;
 +
margin-bottom:10px;
 +
border-radius:30px;
 +
border: 5px solid #007bb6;
 +
overflow:hidden;
 +
background-color:#003F87;
 +
float:left;
 +
}
 +
.box:hover{
 +
box-shadow: 5px 5px 10px #555555;
 +
}
 +
.box img {
 +
margin:50px;  
 +
width:70%;
 +
height:auto;
 +
margin-left:15%;
 +
display:none;
 +
border-radius:10px;
 +
box-shadow:none;
 +
drop-shadow:none;
 +
}
 +
.box p {
 +
font-family:Arial;
 +
font-size:30px;
 +
font-weight:bold;
 +
padding-top:25px;
 +
text-align:center;
 +
}
 +
.popup {
 +
background:#000000;
 +
width:60%;
 +
position:fixed;
 +
top:200px;
 +
margin-left:20%;
 +
height:auto;
 +
border-radius:15px;
 +
border:5px solid #007bb6;
 +
box-shadow: 5px 5px 10px #191919;
 +
}
 +
.popup:hover {
 +
box-shadow: 8px 8px 12px #000000;
 +
}
 +
.popup h1 {
 +
font-size:50px;
 +
font-weight:bold;
 +
width:90%;
 +
margin-left:5%;
 +
text-align:center;
 +
font-family:Arial;
 +
color:#fff;
 +
padding:30px;
 +
background:#F59A2C;
 +
text-shadow: 2px 2px 4px #000000;
 +
border: none;
 +
border-radius:20px;
 +
}
 +
.popup p{
 +
font-size:17px;
 +
color:#fff;
 +
padding:10px;
 +
text-align:center;
 +
font-family:Arial;
 +
}
 +
.popup p:last-child {
 +
font-size:10px;
 +
color:#fff;
 +
width:80%;
 +
margin-left:10%;
 +
height:auto;
 +
text-align:center;
 +
}
 +
.jumbotron p {
 +
font-family:Arial;
 +
font-size:40px;
 +
padding:5%;
 +
}
 +
#ref-button, #ref-button2 {
 +
width: 25%;
 +
 +
height:auto;
 +
display:inline-block;
 +
background:#009dd8;
 +
border-radius:15px;
 +
border: 2px solid #fff;
 +
padding: 2px;
 +
font-style:normal;
 +
text-align:center;
 +
margin-bottom:15px;
 +
margin-top:15px;
 +
}
 +
#ref-button {
 +
margin-left:10%;
 +
}
 +
#ref-button:hover, #ref-button2:hover {
 +
box-shadow:2px 2px 4px #dddddd;
 +
}
 +
#ref-button a, #ref-button2 a {
 +
width:100%;
 +
height:100%;
 +
}
 +
#ref-button p, #ref-button2 p {
 +
font-weight:bold;
 +
padding-top:5px;
 +
color:white;
 +
font-size:13px;
 +
text-transform:uppercase;
 +
text-align:center;
 +
}
 +
#ref-button2{
 +
display:none;
 +
float:right;
 +
margin-right:10%;
 +
}
 +
.active {
 +
//display:block;
 +
}
 +
#ref-content{
 +
display:none;
 +
margin-top:50px;
 +
}
 +
#ref-content h3{
 +
clear:both;
 +
}
 +
#description-wrapper h3 {
 +
color: #fff;
 +
border-bottom:1px dotted #007bb6;
 +
}
 +
#description-text-wrapper h3:first-child {
 +
margin-top:10px;
 +
}
 +
#description-wrapper .minimize,#description-wrapper .maximize {
 +
display:inline-block;
 +
width: 15%;
 +
height:auto;
 +
font-size:10px;
 +
background:#009dd8;
 +
color:white;
 +
border-radius:15px;
 +
border: 2px solid #fff;
 +
padding:2px;
 +
font-style:normal;
 +
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iGEM 2015

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University of Virginia iGEM 2015

House of Carbs

A Novel Solution to Minimizing Postprandial Hyperglycemic Spikes

Project Overview

The Problem: Diabetes Mellitus and Hyperglycemia

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From diabetes mellitus a number of devastating complications, such as amputations, blindness, crippling neuropathies, and many others, can arise from increased blood sugar levels on a regular basis, but many of the major complications of diabetes arise from drastic fluctuations in the blood glucose level (Ceriello et al., 2012). Up to two-thirds of people with diabetes die of cardiovascular disease (CVD) brought about by diabetes-related macrovascular diseases (Deshpande et al. 2008). In fact, the risk for cardiovascular disease mortality is 2 to 4 times higher in people with diabetes than in people who do not have diabetes. Additionally, diabetic retinopathy is the most common microvascular complication among people with diabetes and results in more than 10,000 new cases of blindness per year. Retinopathy is associated with prolonged hyperglycemia; it is slow to develop, and there is some evidence that it can begin to develop as early as 7 years before clinical diagnosis of diabetes (Deshpande et al., 2008).

Postprandial (post-meal) blood sugar spikes specifically are one of the most damaging complications of diabetes (Parkin et al., 2002). Many diabetics are able to effectively manage post-meal glycemic spikes with self-administered doses of insulin, but these hyperglycemic incidents still kill more Americans per year than any other diabetes-related complications (Parkin et al., 2002). Arguably, the gravest consequence of glycemic spikes in diabetes patients is the development of progressive macrovascular disease (MVD), which affects the large blood vessels of the body, hardening and blocking these vessels (Ceriello et al., 2012). MVD is the leading cause of death among T2DM patients in the United States, causing up to 65% of diabetes-related deaths, making it a huge target for diabetes treatments research (Deshpande et al., 2008). MVD also frequently leads to other severe complications such as ischemia in the extremities and blindness (Haffner et al., 1998).

Controlling Hyperglycemic Spikes

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For many T1DM and T2DM patients, it has been shown that the regular control and management of blood glucose levels prevents many of the vascular complications of the disease, but most of the time control over glucose is difficult to attain because the self-dosing insulin treatment system that a lot of moderately to severely sick diabetes patients use is often hard to calibrate and use (Parkin et al., 2002).

Compared to sucrose-rich food, starch-rich food has been found to create less fluctuation in blood glucose levels, and thus is beneficial to diabetes patients and hyperglycemia patients. There is evidence that this flatter response caused by a starch rich meal is associated with the slower rate of digestion of complex sugars versus simple sugars (Jenkins, Wolever, & Jenkins, 1988). Thus, if some of the simple sugars are first converted into complex saccharides inside the E. coli and then released back into small intestine, a similar flatter glycemic response will take place, which will be beneficial to the patients.

Our Devices

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We have assembled one plasmid with genes that dictate a controllable level of simple sugars uptake and one plasmid to produce glucan and fructan from simple sugars and then lyse to release the complex sugars back into the environment. In essence, this microbial device runs on two genetic devices -- an uptake circuit and a polymerization circuit.

In order to learn more details, please visit the Project page.

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References

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