Uncovering a potential causative agent of Crohn's disease - Mycobacterium avium paratuberculosis

Institute for Genome Sciences at the University of Maryland School of Medicine
Baltimore, Maryland
BiologyMedicine
$200
Pledged
10%
Funded
$2,000
Goal
4
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  • $200
    pledged
  • 10%
    funded
  • 4
    days left

About This Project

There is speculation that the bacterium, Mycobacterium avium paratuberculosis (MAP), is a causative agent of Crohn's disease (CD). Current diagnostic techniques for MAP are poor. Therefore, it is crucial that we devise new assays to detect for MAP in CD patients. To gain insight into the relationship between MAP and CD, we must sequence the MAP genome and isolate it from CD patient blood. Genomic isolation techniques include PCR amplification and the novel use of hybrid capture probes.

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What is the context of this research?

Crohn's disease (CD) is a form of Inflammatory Bowel Disease (IBD) that impacts approximately 700,000 Americans. While there is no known cause for CD, Mycobacterium avium paratuberculosis (MAP) has been proposed as a causative agent. This bacterium is known to cause a gastrointestinal condition in ruminants, called Johne's disease, which has striking similarities to CD. In previous studies, MAP has been shown to be significantly more prevalent in patients with CD (see https://www.ncbi.nlm.nih.gov/p...). Past research, however, has not been able to pinpoint this higher incidence as being causative or correlative. Gathering sufficient genomic data to demonstrate the influence of MAP in CD would greatly advance efforts to find a cure, which remains elusive.

What is the significance of this project?

MAP is a gram-positive, mycobactin dependent, obligate pathogen. The bacterium is routinely spread throughout dairy and beef herds as it is sub-clinically shed from infected cattle. The pathogen can survive pasteurization and chlorination techniques, showing that MAP may be present in our dairy, water, and beef supplies. Crohn's disease, which is the potential result of a MAP infection, is oftentimes debilitating. Symptoms include gastrointestinal bleeding, weight loss, fatigue, stomach pain, and diarrhea. If complications persist, CD can be fatal. Due to the severe nature of Crohn's disease, it would be beneficial to uncover the relationship MAP plays in the condition. Sequencing of the MAP genome is the first step to understanding this relationship.

What are the goals of the project?

The goals of this project are to sequence the MAP genome and then develop a set of methods for the identification of the bacterium, Mycobacterium avium paratuberculosis (MAP), in blood samples obtained from patients with Crohn’s disease. First, we will obtain samples of MAP that have been successfully cultured from blood samples of CD patients. We will then extract DNA from these samples and sequence the MAP genome. After sequencing, we will design a set of MAP-specific PCR primers and use these to PCR amplify MAP. Additionally, we will PCR amplify MAP directly from CD blood samples, as well as design a set of MAP-specific hybrid capture probes, bypassing the need to grow MAP in culture.

Budget

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The primary focus of this research project is to isolate the DNA of MAP so that its genome can be sequenced. After doing so, MAP-specific primers will be designed so that we can attempt to PCR amplify it from the blood of patients with Crohn's disease. Additionally, hybrid capture technology will be used to test for MAP in patient blood. These goals, which may later prove MAP to be the causative agent of Crohn's disease, are only possible if the genome of MAP is sequenced first.

Endorsed by

This is an opportunity to use new genomic techniques to look for the fingerprints of Mycobacterium avium paratuberculosis (MAP) in clinical specimens from known Crohn's disease (CD) patients. Consistent detection of MAP may add to the current evidence that MAP plays a role in the pathogenesis of Crohn's disease and perhaps assist in the treatment.
This proposal takes steps to address a critical need in Chron's disease - following leads to define causative agents. A genome sequence will allow the researchers to determine the 1) presence or absence of MAP in Chron's patients and 2) its prevalence in the general population, which provides the impetus for causation studies. Dr. Beurmann is ideally qualified to mentor this work as she has already conducted similar studies with coral pathogens. The results of this study have the potential to contribute greatly to the field.
Jacob is an outstanding undergraduate at the University of Maryland who has the scientific skills and personal incentive to carry out this project on sequencing the genome of Mycobacterium avium. This genomic sequence will be a significant contribution to the research effort to understand the biological basis of the enigmatic disease called Crohn's disease.
The significant impact on the quality of life Crohn's disease has on individuals is reason enough to warrant further investigations into its etiology and the development of diagnostics. This project seeks to answer an important question that may seem simple at face value, but will be a complex process has the potential for profound ramifications on human health. I have collaborated with Dr. Beurmann on identifying several novel etiological agents of disease, therefore, I am confident this project is in able hands and fully endorse this work.

Flag iconProject Timeline

By early July, we will have extracted DNA from samples of MAP that our collaborator successfully cultured from blood samples obtained from Crohn's patients. Following this step, we will sequence the MAP genome and design MAP-specific PCR primers by mid-late July. By mid August, we will attempt to PCR amplify MAP and use hybrid capture probes on the blood of patients with Crohn's disease, in order to determine if MAP is present within patients that have Crohn's disease.

Jun 29, 2017

Project Launched

Jul 07, 2017

Obtain MAP samples and extract DNA

Jul 14, 2017

Sequence MAP Genome

Jul 28, 2017

Design and test MAP-specific PCR primers

Aug 11, 2017

Use hybrid capture probes and PCR amplification to detect for MAP in the blood of patients with Crohn's disease

Meet the Team

Jacob Friedman
Jacob Friedman
Undergraduate Intern

Affiliates

University of Maryland Baltimore Institute for Genome Sciences
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Silvia Beurmann
Silvia Beurmann
Postdoctoral Research Fellow

Affiliates

University of Maryland Baltimore Institute for Genome Sciences
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Jacob Friedman

I am a rising sophomore in the Honors College at the University of Maryland-College Park. I am a Biology major with a concentration in ecology and evolution. My other academic passions include genetics, microbiology, cellular biology, and environmental science. I aspire to attend medical school and become an orthopedic surgeon, immunologist, or gastroenterologist.

This summer I am working at the Institute for Genome Sciences at the University of Maryland School of Medicine under Dr. Claire Fraser. We will be studying the pathogen Mycobacterium avium paratuberculosis (MAP) as a possible causative agent of Crohn's disease. I was diagnosed with Crohn's disease in April of 2014 and am very familiar with the symptoms, biology, and patterns of the disease. As an aspiring biologist and someone who has firsthand experience with Crohn's disease, I am dedicated to discovering the role MAP plays in Crohn's.

Silvia Beurmann

Born and raised in Switzerland, I received a B.S. in Biology and Biochemistry from the University of Zurich in 2010. After graduation I completed an internship focusing on the health state of the Seychelles' coral reefs. Afterwards I moved to Honolulu, Hawai‘i, where I enrolled in the Ph.D. program in Microbiology specializing in Marine Biology. I investigated the coral disease Montipora White Syndrome and the pathogenic bacteria associated with this disease. I then decided to change my field of study and apply my learned skillset to the human disease field, investigating the human gut microbiome.

Lab Notes

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Additional Information

This work will provide the foundation for expanded studies to investigate the potential role of MAP as a causative agent in Crohn's disease. Our work may provide the foundation for a cure for Crohn's to be discovered.


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