Protein Evolution
Researchers are making extraordinary progress by applying ever better sequencing technologies to biological problems. This is particularly true of DNA and protein sequencing. The linear sequences of nucleic acid bases and amino acids constituting the building blocks that provide this kind of essential information for every known variety of life is extraordinary. We have trillions of these building blocks of sequence. But the sequence is only part of the answer. DNA does not exist only as a sequence and neither do proteins. They interact and influence each other with evolutionary consequences.
Alexey Porollo, PhD, with gifted undergraduate, Frasier Baker, published a new informatics tool, called CoeViz, which finds pairwise changes in the amino acid structure of a protein. This means that if a certain amino acid is changed in a certain way, then the new approach predicts what second changes would occur at another amino acid which would be likely to preserve the critical function of that protein. This approach provides insight into evolutionary alterations in proteins of different species.
Super-women in Autoimmunity
You know that nearly all men have an X and Y chromosome, and women have two X chromosomes. Did you know that one in a thousand women has three X chromosomes? These super-women tend to be about an inch taller than women with only two X chromosomes, but usually they are in the normal range for most everything else. Ke Liu, PhD, Ken Kaufman, PhD, Leah Kottyan, PhD, and John Harley, MD, PhD, along with 75 collaborators from around the world collected patients with systemic lupus erythematosus and a dry eye and mouth disease called Sjogren’s syndrome; both are predominately female diseases 1:10 and 1:20, respectively, male to female. As predicted, the super-females with three X chromosomes have both of these disorders at a higher rate than women with two X chromosomes, consistent with the idea that the number of X chromosomes influences the risk for these diseases where men with one have a much lower risk than women with two who are also at a lower risk than these super-women with three.
Matt of All Trades
Transcription factors help decide what cell and when genes are expressed. This happens when scientists copy the DNA code to the RNA. Then the RNA influences what the cell does on its own or it translates into proteins. These transcription factors, and what they do, are at the center of much of the progress now made in medical research.
Matt Weirauch, PhD, has made himself an expert in this area of biology. He has had the critical informatic role in expanding what we know about the DNA sequences that these proteins bind, and has found himself involved in a wide variety of different projects that are all biology. For example, he not only helped the group headed by
Rafi Kopan, PhD, in the
Division of Developmental Biology to develop a new method which would reveal when transcription factors were working very close to each other on the genome, the deeper meaning of the actions of PLZF, and worked on the sequences of DNA that particular transcription factors prefer; but he also helped interpret the genomes of both a plant
(Arabidopsis thaliana) and of bed bugs. This is a scientist with abiding curiosity into all forms of life on earth.
Success with extramural funding of research
Sue Thompson, PhD and Leah Kottyan, PhD both have done their part for the Center for Autoimmune Genomics and Etiology (CAGE) by bring wonderful success in the very competitive world of grant funding. Sue managed to renew the funding that provides infrastructure for the investigative commitment that Cincinnati Children’s has traditionally made to juvenile idiopathic arthritis. This will provide support for many new projects meant to understand and treat this condition better than we have in the past. Leah has led a long term collaboration with the Allergy Division for the genetics of eosinophilic esophagitis. These children have swelling and edema of their esophagus to the point that they cannot swallow. Success with this project has been made possible by the infrastructure composed by her collaborator, Marc Rothenberg, MD, PhD. The studies to follow their discoveries are so compelling that she was awarded support as the Principal Investigator by the National Institute of Allergy and Infectious Diseases to pursue these new ideas for the next five years.
New Ideas Must Run the Gauntlet Before They are Accepted
Steve Waggoner, PhD, has been disrupting our thinking for a number of years now with the idea that a kind of immune system cell called “natural killer” cells actually act to inhibit our own immune responses. Many scientists had their doubts, and it required years of experiments to convince them. If we had the capacity to manipulate this phenomenon, then we might be able to help the body cure chronic infections like HIV, the human immunodeficiency virus, or some cancers; or going in the other direction, inhibit destructive autoimmune responses in thyroid disease, lupus or rheumatoid arthritis. Dr. Waggoner has had a major role in showing that these natural killers modulate immune responses; ideas that have not been easily accepted by our professional scientific colleagues. In the past year, he finally reached the point where his ideas published are reviews of progress in the field of immunology, and appear to now be part of the lexicon of accepted knowledge. This is an important milestone in science—when your work is on its way to the textbooks introductory students learn from when first entering a field.
Future
The faculty and staff of the
Center for Autoimmune Genomics and Etiology (CAGE) have at least 40 different scientific initiatives underway. These initiatives promise to provide important future advances for the coming versions of this report, most in ways that we least expect as the montage of progress we assemble will be one where chance favors fertile minds prepared for new discovery.
