Award Description: Sideroblastic Anemia With B-Cell Immunodeficiency, Periodic Fevers, And Developmental Delay (SIFD) Research Project
Grant amount: $53,000 over two (2) years.
Investigators: Martin Holcik, Urszula Liwak-Muir; Turaya Naas; Quinlan Wylie, Hanna Ludwig , Ribal Kattini, Chloe Campbell, Brianna Rino, Romanah Ahmed, Megan Williams, and Angelo Slade*
Sideroblastic Anemia With B-Cell Immunodeficiency, Periodic Fevers, And Developmental Delay (SIFD) Research Project.
This research project aimed to understand the molecular mechanism of why mutations in a gene called TRNT1 cause this rare but devastating mitochondrial disease. TRNT1 is an essential enzyme that modifies all tRNAs in a cell; mature tRNAs are, in turn, required for the proper synthesis of all cellular proteins. In particular, the study focused on one aspect of SIFD pathology; the fact that the patient-derived cells are sensitive to oxidative stress. The working hypothesis was that TRNT1 deficiency results in reduced ability to repair tRNA termini and thus increased susceptibility to oxidative stress (and perhaps other stresses as well), thus contributing to the broad phenotype seen in SIFD patients.
The study identified several downstream proteins that are differentially expressed in patient cells. Researchers have further noted that the same proteins are differentially expressed in tissues derived from a mouse model of TRNT1.
This research study providing training for ten (10) trainees, two (2) manuscripts have been published and two (2) are currently being prepared.
*Trainees: Urszula Liwak-Muir (postdoctoral fellow; CHEO RI); Turaya Naas (postdoctoral fellow; CHEO RI); Quinlan Wylie (undergraduate student, CHEO RI), Hanna Ludwig (undergraduate student, CHEO RI), Ribal Kattini (undergraduate student, Carleton), Chloe Campbell (undergraduate student, Carleton), Brianna Rino (undergraduate student, Carleton), Romanah Ahmed (undergraduate student, Carleton), Megan Williams (undergraduate student Carleton), and Angelo Slade (Ph.D. student, Carleton)
Funding details: $53,686.81 per year for 2 years .