What my lupus research project is

Now that we’ve gone through the introductions, here’s a little bit about the project I’m working on (I promise it will be understandable!). I am examining the role of a lupus-associated gene, called PTPN22, in response to viral infection. Many people with lupus, and other autoimmune diseases such as rheumatoid arthritis, have a mutation in this gene and produce a mutated protein. This protein’s mutation is in the form of a substituted amino acid at position 620.

What does that mean? Genes code for proteins–the sequence of base pairs in the DNA, like a barcode, are scanned by molecules in the cell to then produce a protein. Imagine a string of beads, and each bead can be one of around 20 different colors. The beads represent the amino acids–building blocks of proteins–while the different colors represent different kinds of amino acids. You may have heard of some of them. The amino acid phenylalanine is used to make the artificial sweetener aspartame, for instance. The mutation in the PTPN22 gene can be represented as an incorrect line in the barcode. A string of beads will still be produced, but the 620th bead will be the wrong color, say a red bead instead of a blue bead. This is the amino acid substitution at position 620.

What is the significance of this mutation? Mutations happen all the time, and sometimes they are harmless. This is because each amino acid can be coded for by more than one three-base pair sequence. So a mutation in the DNA might just make the same amino acid, and there is no change in the protein. Sometimes mutations turn a sequence of DNA into nonsense, so the protein is not even produced. Finally, as in the case of PTPN22, a single base pair mutation very slightly changes the resulting protein. The protein is still produced, but its function might be impaired. PTPN22 appears to have a role in the production of a chemical messenger produced by white blood cells, called type 1 interferon. This is significant because altered levels of type 1 interferon have been associated with SLE, causing inflammations in certain regions such as the kidneys and joints. The normal function of type 1 interferon production is crucial for a healthy response to infection, such as a viral attack.

My question addresses this directly. I am asking “what is the role that the lupus–associated mutated version of PTPN22 plays in response to lymphocytic choriomeningitis virus infection?” To answer my question, I will be looking more specifically at the PTPN22 gene which is housed within DNA and will be evaluating the activation of certain white blood cells that respond to type 1 interferon. The activation of these white blood cells is essential for an efficient response to infection.

Based on previous work done by Dr. Peterson’s lab, I expect to see a reduced response in SLE-associated form of PTPN22. I look forward to writing more about how the experiments are going, and also to presenting my results at the end of August!


About the Author:

2012 Student Summer Fellow Pietro Miozzo, from New York, New York, will be a sophomore at Yale University in the fall. Pietro is studying molecular, cellular and developmental biology in the pre-med program there. Pietro is working in Dr. Erik Peterson's lab in the University of Minnesota's Center for Immunology Research this summer, looking at the development and function of immune cells that have been implicated in a number of autoimmune diseases. The group is looking at the function of a powerful lupus-predisposing gene, and its role in potentially altering the functions of cells in fighting infections and in suppressing the activation of lymphocytes with capacity to damage skin, joints, and other tissues in lupus.
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