Grants Maximize the Potential of Pair of Biochemistry Investigations

Two faculty members in the School of Natural Sciences and Mathematics at The University of Texas at Dallas have received federal grants to support their investigations of how essential elements contribute to both normal physiology and diseased states.

The Maximizing Investigators’ Research Award for Early Stage Investigators (ESI-MIRA) is unlike a traditional research grant. MIRA-supported investigators have the flexibility to pursue the science they’re interested in as it evolves, rather than being tied to one specific project.

Awarded by the National Institute of General Medical Sciences, a component of the National Institutes of Health, MIRAs are a part of the strategy to bring innovation and risk-taking back to basic medical research.

The grants will provide Dr. Sheel Dodani BS’07 and Dr. Gabriele Meloni, both assistant professors of chemistry, each about $1.9 million over five years.

Meloni’s research focuses on gaining a better understanding of how transition metals — both essential trace nutrients, such as zinc, copper and iron, and toxic metals, such as cadmium and lead — are transported in and out of cells.

“Many essential biological processes rely on essential metals,” Meloni said. “On the other hand, metal complexes such as toxic platinum compounds have been exploited as very effective drugs to treat particular types of cancers.”

Because transition metals are chemically reactive, living systems have developed a sophisticated set of proteins to control their homeostasis. Among those, transmembrane transporters coordinate selective movement of metals in and out of cells across cellular membranes to meet indispensable cellular requirements without reaching toxic levels. Dysregulation of cellular metal levels underlies several pathologies, including cancer and neurodegenerative disorders, Meloni said.

The ESI-MIRA grant will allow Meloni to investigate several classes of transmembrane transporters present in human cells and in pathogenic bacteria and better understand their role in physiology and drug resistance.

“Transmembrane transporters have been a hot research topic in the past four decades, but they are typically very challenging to study due to their intrinsic hydrophobic nature,” Meloni said. “Our group has developed several techniques — biochemical, biophysical and structural — to study how these proteins function at a molecular level in purified samples and in artificial membrane systems that we can precisely control. We believe that obtaining insights into their unique structural and functional properties will contribute to the molecular understanding of how the homeostasis of trace elements and metal-based drugs is selectively controlled in cells.”

Dodani’s ESI-MIRA funding will support her work to develop optical-imaging tools to study the roles of negatively charged ions, or anions, in living systems. It is well-known that positively charged ions, or cations, play an essential role in biology, whereas anions are thought to be supporting ions essential only for charge balance or structural integrity when combined with cations.

“Let’s consider table salt,” Dodani said. “It is made up of two ions: a positively charged sodium and a negatively charged chloride; however, if we look at a nutrition label, we will only see sodium listed. What about the chloride? It is the most abundant anion in our bodies. If we could capture a molecular-level picture of what chloride and other anions are doing in living cells, we could better understand how we can control levels of anions to control diseased states, including cystic fibrosis, autism and chronic pain.”

Dodani said that if she and her team can develop a robust set of tools to visualize anions like chloride in living cells, it would revolutionize the way researchers look at the roles of both cations and anions in biology.