Undergraduate Research Opportunity
Accepting Applications for the 2018 Calendar Year
Application Deadline: November 27, 2017
This project is a partnership between the University of Illinois at Urbana-Champaign
and Millikin University, Decatur, IL.
Funded by the National Institute of Dental and Craniofacial Research, National Institutes of Health
Program title:
Genome Data Mining and Laboratory Experimentation to Reveal the Fungal Agglutinin-Like Sequence Family
Applicants:
- Pre-Dental students are especially encouraged to apply.
- Six undergraduate students (sophomores and juniors) will be selected to participate in this opportunity.
What are the benefits of participating in this program?
You will learn:
- Genome sequence analysis techniques
- Molecular biology laboratory skills
- Research ethics and compliance information
- Scientific writing, leading to production of an abstract and poster to present at a scientific meeting and a manuscript for publication
You will earn:
- Research credits during spring and fall semesters 2018
- A total of $4800 as an hourly employee during the 12-week summer program
What Will I Study?
The Agglutinin-Like Sequence (ALS) gene family in fungi!
The ALS gene family was first characterized in Candida albicans, a fungus that causes a variety of diseases including orophyaryngeal candidiasis (OPC). OPC is one of the initial clinical signs that a person infected with HIV has developed AIDS. OPC can also affect infants and people who wear dentures.
Classic presentation of oral candidiasis. Note growth of the fungus on the surface of the tongue. (Image from https://en.wikipedia.org/wiki/Oral_candidiasis)
Immunolabeling of the surface of a C. albicans germ tube with monoclonal antibodies that are specific for a particular Als protein (e.g. Als1, Als3 or Als4). Note the obvious cell-surface localization of the proteins and their specific locations on the germ tube surface. (Image from Coleman et al., 2012. FEMS Immunol Med Microbiol 64:321-333).
ALS genes encode large cell-surface glycoproteins that are involved in adhesion of the fungus to host surfaces and abiotic surfaces that are covered in proteins such as saliva or serum. The long-term goal of the laboratory’s work is to determine if the Als proteins can be exploited to reduce fungal adhesion to oral surfaces and decrease the opportunity for disease to develop. The first step in this process is to determine how many Als proteins are present and the sequence of the genes that encode them. Sounds simple, right?
Well…there is one little issue with ALS gene sequences that makes them difficult to assemble in genome data: ALS genes contain a central domain of highly conserved, tandemly repeated DNA. Think of the ALS coding region as consisting of three parts like a human figure: a head, a torso and legs. The tandem repeats are the torso and nearly identical torsos are found in numerous genomic locations. Therefore, it is difficult to determine which heads match which legs and which torsos fit between them. Laboratory experimentation is required for correct assembly of the gene sequences.
A cartoon of the ALS gene family, with each gene depicted as a human figure. For the purpose of this illustration, each gene is considered to be made of three domains (e.g. a head, torso, and legs). The torso in each gene is a region of tandemly repeated DNA sequences, which can be many kilobases in length. Because there are many loci that contain these repeated sequences, assembly of the ALS genes using automated methods often fails. (Image by Kerry Helms, The Design Group @ Vet Med; published in Hoyer et al., 2008. Med Mycol 46:1-15).
A cartoon showing the consequences of poor automated assembly of ALS gene sequences. This drawing shows the resulting loci predicted from the initial assembly of the C. albicans genome sequence. A total of 12 independent ALS loci were predicted from the genome sequence, when in fact the genome encodes only eight ALS loci. Laboratory experimentation was required to determine the correct ALS gene assembly. (Image by Kerry Helms, The Design Group @ Vet Med).
Other fungi in addition to C. albicans cause OPC and the ALS genes are not assembled accurately in these published genome sequences. The example of ALS genes from Candida tropicalis is shown below. How many distinct loci are there? What is the accurate sequence for each locus? How do the answers to these questions compare to the composition of the ALS family in other OPC-causing fungi? Those questions are at the center of the project that we will complete.
A schematic showing one of the many genome puzzles that need to be solved in the context of this project. The figure shows the status of the ALS gene family assembly in the current published genome sequence for the fungal pathogen Candida tropicalis. While some sequences may be assembled correctly (e.g. 00941), others are essentially missing ‘legs’ (e.g. 01028) or a ‘head’ (e.g. 03787). Some ‘torsos’ are disconnected from the corresponding head and legs (e.g. 03788). How many ALS loci are encoded by C. tropicalis? The answer could be as many as 18, but likely is fewer once the various sequences are assembled correctly. If you like solving a challenging puzzle, this project is for you!
If you want to learn more about the ALS gene family and Als protein function, you can view a recent review article here.
Do you want to apply for this program?
If yes, complete the following three steps no later than Monday, November 27, 2017:
- Request a letter of reference from two different people who are familiar with your performance as a student and/or scientist. Have each letter sent to: R15_Pro.a6l3fijhbsdd5gxc@u.box.com. Each letter writer should receive e-mail confirmation that their letter was received successfully.
- Read the program agreement. Indicate that you agree to the program’s standards and requirements by completing this form.
Once you finish this last step, your application is complete.
Please send questions about the program to Dr. Lois Hoyer.