Ask Mikael Elias about his research interests and you may be surprised by his response. The researcher offers up a wide-ranging list of topics from reducing wound infections to protecting crops from pathogens and removing excess fertilizer components from water. His investigative inclinations are unusually broad. But for Elias, it’s all in how you look at things. In his case, that means adopting an enzyme-based perspective.
Hired as part of the University’s MnDRIVE initiative, Elias joined the faculty of the Department of Biochemistry, Molecular Biology and Biophysics, and the BioTechnology Institute earlier this fall. His research focuses on characterizing enzymes from extremophiles – single-celled bacteria and archaea that survive in harsh environments. He has chosen this specialized group of organisms because their enzymes are tailor-made to withstand extreme conditions and are likely to be more stable in downstream applications because of it. Ultimately, he intends to use the results as a springboard for biomedical, environmental and agricultural applications.
Elias’ current work began in earnest when he questioned the validity of a 2010 NASA study claiming the discovery of a bacterial species that can survive on arsenate, a form of the element arsenic and one that is poisonous to life because it looks nearly identical to the biologically-necessary chemical phosphate. “They were claiming it was a new life form,” Elias says. “Many people saw this paper and got upset. When I saw this paper, I got the idea to review what was already known about enzymes that use phosphate as a substrate.” He found that none of that group of enzymes were able to discriminate arsenate from phosphate, so he set out to understand how the bacteria do survive.
Elias knew the organisms had to have some mechanism that allowed them to use phosphate to resist the poisonous arsenate in the lake where they lived. He reasoned that this mechanism could be found in a phosphate uptake protein, a cellular bouncer of sorts that recognizes phosphate and lets it in while keeping arsenate out. The next step was to figure out how. Elias identified the structure of the protein when paired with phosphate and determined that, unlike all other known phosphate binding enzymes, this one can distinguish the incredibly tiny difference between the two very similar chemicals. One atom in phosphate is less than one ten billionth of a meter displaced from its arsenate counterpart, and the enzyme uses a previously undiscovered type of chemical bond to sense out the different substrates. His findings were published in the journal Nature and were the topic of many popular science articles.
The researcher has since moved on. He’s currently investigating mutant forms of the phosphate uptake enzyme that may potentially be used in phosphate bioremediation and, ultimately, as a way of regenerating sources of the increasingly scarce nutrient.
Elias knows that extremophiles are a largely untapped source of other potentially useful, stable enzymes, thus he also plans to identify and characterize others in his lab. He has already begun to study an enzyme that degrades quorum sensing molecules, or molecules that bacteria use to communicate with each other. Because pathogens often take a strength-in-numbers approach to infection, they wait until enough bacteria are around — indicated by the level of quorum sensing molecules — before they start a coordinated attack on a host’s immune system. Furthermore, they often do so by forming a biofilm, a complex structure that renders the bacteria in it less susceptible to attacks from the immune system, or drug interventions such as antibiotic treatment. His research has already shown that a topical application of pure enzyme can reduce biofilm formation in a rat pneumonia model as well as in the ocean.
Elias was drawn to the University of Minnesota because he feels that pursuing research projects with faculty in many different departments is not only encouraged, it is the norm. “Here you have synergistic interactions between people in different fields, so I have already learned about collaborations with biochemists and biologists and mechanical engineers,” Elias says. “The only limitation is what you have in your own head.”
— Sarah Perdue