18desilvni (Talk | contribs) |
|||
Line 146: | Line 146: | ||
/></a> | /></a> | ||
− | <a href="#project-design"> | + | <a href="#project-design">Overview</a> |
<br> | <br> | ||
− | <a href="#part-design"> | + | <a href="#part-design">Understanding the Problem</a> |
<br> | <br> | ||
− | <a href="#experimental-design"> | + | <a href="#experimental-design">Identifying Thymol</a> |
<br> | <br> | ||
− | <a href="#future-directions"> | + | <a href="#future-directions">Part Design </a> |
<br> | <br> | ||
− | <a href="#understanding-the-problem"> | + | <a href="#understanding-the-problem"> Experimental Design</a> |
<br> | <br> | ||
− | <a href="#experimental-troubleshooting"> | + | <a href="#experimental-troubleshooting">Future Directions</a> |
− | |||
− | |||
<br> | <br> | ||
<a href="#references"> References</a> | <a href="#references"> References</a> | ||
Line 358: | Line 356: | ||
</div> <!--Everything above this is in the ACCORDION. So copy and paste a new experiment above here. --> | </div> <!--Everything above this is in the ACCORDION. So copy and paste a new experiment above here. --> | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
</div> | </div> | ||
<hr> | <hr> |
Revision as of 22:24, 27 October 2020
OVERVIEW
Optimizing Nutrient Absorption Through Anthelmintics
To allow our target communities to maximize micronutrient and vitamin A absorption in between deworming seasons, we will engineer our yeast to produce thymol which is naturally found in thyme leaves. This will allow our yeast consumers to alleviate damage and destroy parasitic worms in the intestines. Our initial goal is to create a proof of concept in the lab. To do this, we followed the engineering design cycle to build our project:
- Understand the Problem
- Research and Ideate Solutions: Identifying Thymol
- Design Solutions: Part design
- Design Solutions: Experimental design
- Create and Test: Thymol Testing
- Evaluate
Over the next year, we will be working towards a lab proof of concept for thymol testing and production. This engineering design cycle will repeat once we have accomplished this and look towards community implementation. For more information on our plans for next year and beyond iGEM, please refer to the Future Directions section.
UNDERSTANDING THE PROBLEM
Inadequate Access to Healthcare
Mass-supplementation of Vitamin A to deficient regions have been ongoing for decades.However, even with biannual vitamin A supplementation for children and biofortified crops such as golden rice, intestinal parasites still play the villain in preventing the vitamin’s assimilation by perforating the intestines. Organizations such as the UN, WHO, and the Bill Gates Foundation couple biannual vitamin supplementation with deworming using agents like albendazole and mebendazole, but lack of clean water and proper footwear allow these parasites to return and thrive in the intestines.
Parasitic worms are among the most widespread human infections to date, affecting 2 billion people worldwide. The most common of these are Ascaris lumbricoides or the giant roundworm, hookworms, and Trichuris trichiura or the human whipworm. These worms may be obtained from direct contact with the soil, or through improper measures in hygiene. These worms cause a variety of symptoms such as stunted growth, decreased metabolic rates, physical and mental fatigue, and malnutrition (Kumar, Jain, & Jain, 2014). Since these parasites perforate the intestines, nutrition absorption is severely inhibited, causing several micronutrient supplementation programs to falter.
Albendazole has been used as an effective cure for intestinal worm infections. When treating roundworms it has a cure rate of 98.9% and egg reduction rates of 99.6%. For hookworms, it is 56.8% and 97.7% respectively, while in whipworms it is 10.% and 73.3%. However, even with these highly effective drugs the worms return and thrive until the next round of deworming because of poor hygiene due to lack of access to clean water and proper footwear.
Talking to Dr. John Gilleard and Dr. Paul E. Mains from the University of Calgary, we found out that these drugs were first intended for animals but were later implemented in humans. They believe that intestinal parasites will sooner or later develop drug resistances just as they have discovered in sheep and cattle models, which is why development of new treatments should be kept on the radar.
IDENTIFYING THYMOL
Why produce an anthelmintic?
For this part of the project, we initially intended to produce omega-3 fatty acids such as eicosapentaenoic acid (EPA) which has cognitive benefits to improve the nutritional value of our yeast. We learned from Dr. Dia Sanou and Lourlin Ugdiman, two public health experts who have worked in Africa and the Philippines, that producing a safe and supplementary anthelmintic as a temporary measure is a better use of our efforts. That temporary measure would be sufficient until the next round of deworming.
Our team started looking for plant-based compounds with promising effects for anthelmintics against nematodes. We came across thymol, a compound which is the primary component in thyme oil. Thymol has been used with epsom salts to cure hookworm infections in rural schoolchildren as early as 1912. Half a gram would be administered to children ages 1-5 and a gram for those aged 5-10 (Rural School and Hookworm Disease p. 12, 1970). In modern times, the compound can be found in products such as soaps, disinfectants to pesticides, and in anti-inflammatories. It is labeled to be safe for ingestion with “negligible toxicity” by the USFDA in humans. However, in high doses it may cause burning pain in the oesophagus, nausea, abdominal pain, vomiting, and dizziness [CITE DATASHEET].
PART DESIGN
Why produce an anthelmintic?
For this part of the project, we initially intended to produce omega-3 fatty acids such as eicosapentaenoic acid (EPA) which has cognitive benefits to improve the nutritional value of our yeast. We learned from Dr. Dia Sanou and Lourlin Ugdiman, two public health experts who have worked in Africa and the Philippines, that producing a safe and supplementary anthelmintic as a temporary measure is a better use of our efforts. That temporary measure would be sufficient until the next round of deworming.
Our team started looking for plant-based compounds with promising effects for anthelmintics against nematodes. We came across thymol, a compound which is the primary component in thyme oil. Thymol has been used with epsom salts to cure hookworm infections in rural schoolchildren as early as 1912. Half a gram would be administered to children ages 1-5 and a gram for those aged 5-10 (Rural School and Hookworm Disease p. 12, 1970). In modern times, the compound can be found in products such as soaps, disinfectants to pesticides, and in anti-inflammatories. It is labeled to be safe for ingestion with “negligible toxicity” by the USFDA in humans. However, in high doses it may cause burning pain in the oesophagus, nausea, abdominal pain, vomiting, and dizziness [CITE DATASHEET].
EXPERIMENTAL DESIGN
Thoughtful design of experiments
Add a blurb
FUTURE DIRECTIONS
Next Steps
In order to provide a sustainable, community-based solution, we plan to genetically modify Rhodosporidium toruloides, an oleaginous yeast that naturally produces beta-carotene and lipids, to be more robust and resource-efficient. By modifying the yeast to produce cellulase, it can then use common agricultural waste products as an energy source for synthesizing its oil. It can then be eaten as a vitamin A supplement. The yeast strain, while naturally safe and non-pathogenic, will also be genetically modified to include a kill switch for bio-containment, and optimized for oil production.
References
Paper 1