POTSDAM — Fadi Bou-Abdallah describes iron like this: “Can’t live without it, but you can’t live with too much of it.”
“Luckily, our body has developed an exquisite machinery that maintains this delicate balance to avoid the harmful effects of too little iron — anemia or iron deficiency — or excess iron — iron overload or hemochromatosis,” Mr. Bou-Abdallah said.
That idea has underlined his ongoing iron research over the past two decades, in SUNY Potsdam’s chemistry department and at other labs and institutions. And his research is now being funded by a total of $801,077 in grants through 2022.
In September, Mr. Bou-Abdallah received a $414,047 grant from the National Institutes of Health to fund research that characterizes the physical composition and relevance of differing iron proteins in the body. And last month, he received a $387.030 grant from the National Science Foundation to continue studying how different configurations of iron proteins can impact the body’s ability to successfully maintain iron homeostasis, or the stable balance of iron concentrations and distributions throughout the body.
Both grant-funded projects will be collaborative, with SUNY Potsdam undergraduate chemistry and biochemistry students being “fully involved by performing every single experiment proposed in these grant awards,” Mr. Bou-Abdallah said.
“A good portion of these funds will provide SUNY Potsdam undergraduates with summer support and training in modern biochemical and biophysical techniques, as well as in the laboratory skills necessary to address challenging questions in iron homeostasis and iron-related diseases,” he said.
Mr. Bou-Abdallah has been a faculty member at SUNY Potsdam for more than 10 years, first arriving at the institution in 2007 as an assistant professor of chemistry, becoming an associate professor in 2012 and professor in 2017. His general research has focused on the biochemistry of iron proteins, and the key goal for these grant projects is to better understand iron regulation and the role of iron in human health and disease.
To further explore those roles, Mr. Bou-Abdallah and his team of Potsdam undergraduate students and chemistry colleagues from the Villanova University and the University of Pennsylvania will study the body’s iron regulation mechanisms, specifically looking at ferritins. Ferritins are iron-containing proteins that facilitate the storage and release of iron in the blood.
Ferritins are found in most living things, as they act as an iron distributor to some degree. In humans and most mammals, ferritins serve as the main mediator of iron levels — too much or too little iron, as Mr. Bou-Abdallah points out, can lead to serious medical conditions.
Several researchers have previously studied iron distribution and how deregulation may cause overloads of iron in different organs, as well as heart disease and several iron-related neurological conditions, including Parkinson’s, Alzheimer’s, Pick’s disease, Huntington’s disease, Friedreich’s ataxia and ALS.
Ferritins are comprised of two main subunits, and different proportions and arrangements of those subunits are described as isoferritins, which were discovered by scientists more than 80 years ago.
At the molecular level, these variant isoferritins have not been explored in depth, as studying isoferritins requires a system that can model the differences between isoferritin compositions.
Through Bou-Abdallah’s research with his students, a pioneering method of developing large amounts of synthetic isoferritins has enabled a more in-depth look at how the differing structures might impact iron distribution.
Mr. Bou-Abdallah’s team has engineered a plasmid, to create, in this case, isoferritins that have similar compositions to those naturally found in the human body.
“Many research groups around the world have previously attempted this process, unsuccessfully,” he said. “Our novel plasmid design places us at the forefront of innovation and scientific discoveries, and gives us a unique advantage to study these complex protein nanostructures and their implications in various pathological conditions.”
With the NSF grant, the plasmid and resulting synthetic proteins will be further developed and utilized to study the relationships between the structures and functions of various isoferritins.
Though incremental research has contributed to a greater understanding of iron distribution, Mr. Bou-Abdallah emphasized that “the mechanisms involved are still poorly understood.”
Further research, he said, will help develop a fuller picture of iron imbalances and may help inform treatment approaches for patients with iron-related neurological diseases.