LAB MEMBERS

Noelle Ochotny
Graduate Student

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Using yeast as a model system to elucidate the effects of human “a3” and “a4” mutations that result in osteopetrosis and distal renal tubular acidosis (DRTA) on vacuolar-type proton pump (V-ATPase) activity and expression

I am a graduate student in Pharmacology at the University of Toronto. I have been in the Bone Lab since November 2002. It is my hope that our research will help find ways to either treat or cure diseases of bone and connective tissues, such as osteoporosis, osteopetrosis, and arthritis.

V-ATPases pump protons across a variety of biological membranes. V-ATPases are composed of at least 11 subunits. Seven subunits are part of the hydrophobic catalytic core (V1) and the remaining four compose the hydrophobic domain (Vo), which spans the membrane bilayer. The hydrophobic domain contains one copy of the 100 kDa “a” subunit, which is the focus of my research. Mammalian V-ATPase “a” subunit isoforms are “a1” to “a4”. “a3” is expressed primarily in osteoclasts, which are bone resorbing cells, and “a4” is specific to the distal nephron and acidifies urine. In yeast, the “a” subunit ortholog is called Vph1p. There are two “a” subunit isoforms in yeast, Vph1p and Stv1p.

Human “a3” and “a4” gene mutations result in osteopetrosis and distal renal tubular acidosis (DRTA) respectively. Understanding these “a” subunit mutations will elucidate V-ATPase function, and, we hope, suggest methods to correct these diseases in humans.

On a personal note, I am actively working to maintain the health of my bones by exercising with weights three times a week.

Recent Publications

Ochotny NM, Van Vliet A, Chan N, Yao Y, Morel M, Kartner N, von Schroeder HP, Heersche JN, Manolson MF. Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity. J Biol Chem. 2006, ePub. download