Team:Alma/Description
Project Inspiration & Description
Inspiration for the Idea
Our project idea originated as a research proposal written by Brianna Ricker for the Advanced Biochemistry course. Her original research and description is below - it is inspired by a desire to provide people affected by atherosclerosis with a treatment option that is less invasive or harmful when compared to stents or statins. It helps to address an issue that is relevant on a local, state, national and even global scale - heart disease is responsible for 1 in 4 deaths worldwide, while the impact for Michigan can be gleaned from the image below, adapted from data provided by the CDC.
We had a lot of different ideas to pursue as a project - at one point, we had brainstormed over 20 different project ideas. Eventually, this was selected down to only a few, with the atherosclerosis project being among the finalists. We then sought community feedback on these projects, surveying faculty and students at Alma College about this and other ideas. While this project was not the highest scoring, it was the one that excited people the most when it was fully explained (the survey might not have done the project justice in this way) and seemed to be the best choice for Alma's first iGEM team given the nature of the problem, its scope, and the expert feedback we received from others.
Below, you will find a more complete description of the problem and the science around it, as well as an outline of our solution. Elsewhere, you can find out more about how we developed and selected this project with the help of expert feedback, and how we designed the solution.
The Problem: Cardiovascular Disease and Atherosclerosis
Cardiovascular disease is a class of disease consisting of illnesses that affect the heart and blood vessels. This class of disease is the leading cause of death in the United States, responsible for one in every four deaths. Atherosclerosis is a type of cardiovascular disease that begins as macrophages and cholesterol infiltrate arterial walls forming atherosclerotic plaques. The deposits increase in size as more cholesterol, platelets, and leukocytes become trapped in the plaque. Over time the plaques harden, stiffening the arteries, narrowing the arteries, and stunting blood flow. Atherosclerosis significantly increases the risk of other cardiovascular diseases and life-threatening conditions such as: coronary artery disease, heart attack, heart failure, carotid artery disease, stroke, peripheral artery disease, gangrene, aneurysms, and chronic kidney disease. A disease as destructive and influential as this deserves extensive research, effective treatments, and a cure.
Current Treatments
As of now, atherosclerosis can be treated by undergoing radical, often undesirable, lifestyle changes that are frankly unfeasible for the modern human, or a life-long commitment to drugs. The leading type of drug used to lower cholesterol and in turn prevent the formation of atherosclerotic plaques are statins. However, these drugs come with a host of side effects such as headaches, nausea, muscle pain and wasting, increased blood sugar, and liver damage. New research shows that several diseases show a strong connection to the makeup of the gut microbiota, these new connections could allow new types of treatments to be developed involving alterations of the gut microbiota.
The New Solution
Compounds referred to as gut-derived uremic toxins (GDUTs) are produced by strains of bacteria in the guts of individuals with atherosclerosis. GDUTs enter the bloodstream following the breakdown of phosphatidylcholine and carnitine by bacteria in the gut. In the bloodstream, GDUTs promote the expression of atherosclerosis-promoting inflammatory proteins, and infiltrate vascular tissue allowing atherosclerotic plaques to form. Trimethylamine n-oxide (TMAO) is the most well studied GDUT influencing atherosclerosis and has potential to be metabolized into methane gas before it enters the bloodstream. Bacteria capable of metabolizing TMA (the precursor of TMAO) into methane gas exist, but can’t survive in the human gut. However, genetic modification could allow the machinery responsible for the breakdown of TMAO to be implemented into a bacterial strain that can survive in the human gut.