Zinc finger proteins play a major role in the day-to-day life of and are an important part of the human proteome, the entire set of proteins that can be present in the human body. They also repair DNA that has been damaged by carcinogens such as UV radiation or arsenic.
Researchers are trying to predict the effects of arsenic on zinc finger proteins by utilizing approaches from physics, biology and computer science. Their work has been extensively funded by the National Institutes of Health and takes place at the Center for Advanced Research Computing.
While 3 to 10 percent of the proteome is made up of zinc fingers, not all of them have been discovered. Project supervisor Susan Atlas and her team are studying 22 zinc fingers out of a larger list of 71 that they came up with using a bioinformatics pattern-recognition program, she said.
Bioinformatics is the branch of biology that uses computer programming to study fields like genetics.
When people are exposed to high levels of arsenic, it replaces the zinc in their zinc finger proteins and causes them to stop functioning, Atlas said. This creates health problems.
“They go in and make instant repairs to DNA. When insulted, there can be a screw-up in transcription and the wrong protein can be made,” Atlas said. “They are the nurses and doctors, and if they are inhibited they can’t do their job and you can get very sick.”
While arsenic is not a big problem in the United States, it is in developing countries where it is more prevalent in the drinking water.
One of the things the research is working toward is creating an addition to chemotherapy that would temporarily suppress zinc fingers and allow the chemo to finish its work.
“One of the reasons why I’m interested in this is there’s a contradictory idea,” Atlas said. “When people have cancer already, they get chemotherapy and that destroys fast growing cells in addition to cancer cells. The body has a natural response and the zinc fingers try to repair the fast growing cells and the cells the chemo has destroyed.”
Laurie Hudson, a collaborator on the project, said she measures the extent to which arsenic displaces zinc in particular zinc finger proteins. In some types of proteins the zinc is strongly replaced, while in others it barely is.
Meanwhile, Atlas and her team are building a model of the probable outcomes of Hudson’s experiments. If the model turns out to be a good predictor of what actually occurs, it means that they will be able to accurately predict the amount of displacement for every kind of zinc finger protein.
“If you want to treat people, you need to understand how they get sick ... No one has ever predicted how much arsenic affects particular zinc fingers before,” Atlas said.
Results from this project should be available by the end of the summer if not before, Atlas said.
Qufei Gu, a physics doctoral student, said the project combines the components of many disciplines, an approach that is becoming more common and important in academic work.
“One of the elements of such a diverse project is it fosters a greater diversity of thinking about the problem and brings many different ideas together to solve complex problems,” he said. “For UNM it helps to foster diverse research. Some of the techniques we are developing right now for predicting the quantitative probabilities we hope will help future academics as well.”
Daniel Felker, a postbaccalaureate researcher, is also working on the project. Other students who have worked on the project are Daniel Chee, currently a doctoral student at the University of Washington, and Sam Smith, a master’s student in the public health program.
Marielle Dent is a staff reporter for the Daily Lobo. You can reach her at firstname.lastname@example.org or on Twitter @Marielle_Dent.