To Contact Dr. Watt:
Department of Chemistry and Biochemistry
Brigham Young University
Provo, UT 84602

Office: C210 BNSN
Office Phone: 801-422-1923
Fax Number:
Lab Room:
Lab Phone:
Email: rwatt@chem.byu.edu

BIOINORGANIC CHEMISTRY

Biological systems require trace amounts of metal ions to sustain life. Metal ions are required at the active sites of many enzymes and are essential to catalyze some of the most energetically demanding reactions in biology. Unfortunately, these highly reactive metal ions also catalyze deleterious reactions for biological systems if the metal ion is permitted to be free in solution. For this purpose biology has evolved elaborate systems to bind and sequester metal ions in non-reactive environments to prevent these dangerous reactions from occurring. A class of proteins referred to as Metallo-chaperone proteins is responsible for binding metal ions when they enter the cell and transport the metal ions to the appropriate location and finally these metallo-chaperones are involved in inserting the metal into the protein that requires metal for catalytic activity.

The Watt lab is studying diseases that appear to have disrupted metallo-chaperone systems. Chronic Kidney Disease and Alzheimer’s disease are two diseases that fit into this category. Specifically, iron metabolism appears to have been disrupted leading to free iron. When iron is free in biological systems it catalyzes the formation of superoxide, peroxide and hydroxyl radicals (collectively known as reactive oxygen species or ROS). ROS can cleave DNA, damage proteins and damage lipids. Our research efforts have been focused on metabolites that build up in these diseases. We have performed analysis on how these metabolites disrupt iron loading into ferritin, the iron storage protein or transferrin, the major iron transport protein in the bloodstream. In Chronic Kidney Disease, serum phosphate levels increase because the kidneys are not properly filtering phosphate from the bloodstream. Increased levels of phosphate inhibit iron loading into ferritin by forming insoluble complexes with iron causing free iron to form in the bloodstream that eventually catalyze the formation of ROS. We are now focusing on other metabolites to determine if they also disrupt normal iron loading or release of iron from ferritin.

A related project, discovered from the above work focuses on preparing novel materials inside ferritin. Ferritin is a spherical protein with a hollow interior. Ferritin can store up to 4500 iron atoms in its interior and forms mineral particles between 6-8 nm. The size and metal binding ability of ferritin makes it ideal as a bio-nano-reactor to prepare metal nanoparticles of a specific size. We are developing synthetic procedures to make nanomaterials inside ferritin. To date we have prepared iron-molybdate, iron-vanadate and iron-arsenate minerals. We have also prepared iron-platinum, iron-palladium and iron-gold particles. Future work will continue these synthetic procedures and characterize the materials we make for potential nano-magnets, catalysts or quantum dots. We are also working on linking the ferritins to form arrays of the materials we form.