Fralin Life Science Institute

Research Interests:

The conversion of N₂ gas to ammonia is called nitrogen
fixation. Because ammonia is required for the formation of biologically
essential nitrogen-containing compounds, such as a amino acids and
nucleic acids, nitrogen fixation is necessary to sustain life on earth.
Although most organisms cannot fix nitrogen, a select group of
microorganisms called diazotrophs, "nitrogen eaters", can. The process
of nitrogen fixation has agronomic and economic significance because:

• fertilizer nitrogen is not abundantly available and limits crop production
• is environmentally detrimental
• is an economic drain for farmers

The Dean lab is using molecular biology approaches (e.g., site
directed mutagenisis) to understand how an enzyme called nitrogenase
allows diazotrophs to generate ammonia from N2 at ambient temperature
and pressure (industrial production of fixed nitrogen can only be done
under extraordinarily high temperature and pressure). It is now known
that nitrogenase contains a metal site for binding and reducing N₂, called the iron-molybdenum-cofactor. Two immediate challenges are to:

• determine where and how N₂ becomes bound to iron-molybdenum-cofactor to prepare it for reduction to ammonia.
• understand how iron-molybdenum-cofactor is acquired, assembled and
  inserted into the nitrogenase since free iron and free sulfur within
  the cell are highly toxic

Dean and his colleagues discovered that iron and sulfur are each
processed by a specific protein, NifU and NifS respectively. The
functions carried out by these proteins appear to represent mechanisms
for metabolism of iron and sulfur for all organisms, including humans.
Using yeast as an experimental model, other investigators have now
shown that these proteins are necessary for mitochondrial function.
Genetic defects that affect their activities may turn out to be
traceable to debilitating and usually fatal metabolic disorders
including sideroblastic anemia, ataxia, and cardiomyopathy.