Team:Hong Kong HKUST/modelling

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  • Worldwide obesity has nearly doubled since 1980, while in 2008, more than 1.4 billion adults, 20 and older, were overweight. In particular, many low- and middle-income countries face “double burden” of under-nutrition and obesity. Rates of malnutrition is much higher in low income countries, while there is a greater exposure to high-sugar, high-fat, high-salt foods which are low in cost and nutrients. Such dietary patterns result in low levels of physical strength and sharp increase in childhood obesity with under-nutrition existing side-by-side.

  • 2. In obesity, fatty acids delivered to liver may outpace fatty acid oxidation in hepatocytes, resulting in triglyceride accumulation. Obesity leads to health hazards, including cardiovascular disease - mainly heart disease and stroke, diabetes, musculoskeletal disorders, especially osteoarthritis – a highly disabling degenerative disease of the joints, and cancers, such as endometrial, breast and colon cancers. Combined: http://www.healthcentral.com/common/images/1/19473_13187_5.jpg Cardiovascular: Obesity and other health conditions associated with obesity, including hypertension, insulin resistance, diabetes and hyperlipidemia, are risk factors of cardiovascular disease. http://www.beltina.org/health-dictionary/obesity-cardiovascular-disease-bmi-table.html Diabetes: Patients with type 2 diabetes are insulin resistant, in which high levels of blood fats, cholesterol and triglyceride levels inhibit cells from absorbing blood sugar needed. http://www.bubblews.com/news/560642-cause-of-type-2-diabetes Musculoskeletal disorders: Those with a body mass index (BMI) greater than 26.4 had rate of osteoarthritis of the knees 6 times greater than those with a body mass index of less than 23.4. (Ref. J. Rheumatol. 20 (2) 331-5) http://pharmaworlds.com/obesity-a-growing-burden-for-physicians-and-patients/

  • The fundamental cause of obesity is an energy imbalance between calories consumed and expended. To increase expenditure of fatty acids (calories), HKUST 2013 Team aims to introduce glyoxylate shunt as an artificial futile cycle in HepG2 cell.

  • Part 1 Sense Fatty Acids: We investigated four different sensing mechanisms using: 1) fatty acid metabolism regulator protein (FadR), 2) peroxisome proliferator-activated receptor-alpha (PPAR-alpha) 3) liver- fatty acid binding protein (FABP1) and 4) binding immunoglobulin protein, HSP5 or glucose regulated protein (GRP78). The four sensing mechanisms were measured and compared.

  • Part 2 Introduce Glyoxylate Shunt: We introduced two key enzymes of glyoxylate cycle: isocitrate lyase (ACEA) and malate synthase (ACEB), which allow plants and bacteria to use fatty acids as a substrate for gluconeogenesis. Here, the amount of fatty acids was measured to compare fatty acids uptake rates of cells expressing glyoxylate shunt.

  • Integration of Parts: The integration of sensing mechanism and glyoxylate shunt allows inducible glyoxylate shunt, in which the high levels of free fatty acids in the medium increase fatty acid uptake rate of glyoxylate shunt.

  • Although the problem of malnutrition may remain unsolved, the inducible glyoxylate shunt introduced to mammalian cell increases consumption of fatty acids, lowering the risk of excessive fat accumulation that presents risk to health.




Interview

To discuss the possible safe application of our project, we have met with prominent individuals in Hong Kong society. Through the interviews, we could gain better understanding of our project could actually work as a product.

Presentation

Presentation is one way to share information about project and iGEM to other people, whether it is to fellow academics or to the general public. Find out more about our past and upcoming presentation on synthetic biology.

Gene Therapy Article

It is necessary to think about how our project could be actually applied. Since gene therapy was mentioned as a mean to deliver our DNA into human liver cells, we thought it was necessary to research on the current gene therapy technology.

Videos

We have made several videos to inform the general public about synthetic biology and our project. We tried to make the contents relatively easy so that people with no biology background understand the content.

Country Profile

This is a novel human practice project that we did. We thought it was necessary to gain information of synthetic biology in Asian countries to have a holistic view of synthetic biology around the world.

Blog

While working on the Country Profile, we couldn’t find any webpage or blog specifically made to inform people of synthetic biology. So, we decided to make a simple, but interactive blog for the public in Hong Kong written in Cantonese