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The roles of ubiquitin signaling in fundamental DNA-dependent processes .

ABG-93435 Thesis topic
2020-09-03 Salaire à négocier
Université de Montréal
Montréal - Canada
The roles of ubiquitin signaling in fundamental DNA-dependent processes .
  • Biology
biochemistry, molecular biology, chromatin, transcription, epigenetics, UBIQUITINATION, Molecular Oncology, Deubiquitination, DNA damage and Repair

Topic description

Subject of the thesis: Biochemical and Functional Characterization of BAP1 Deubiquitinase-Interacting Partners: Implications for Chromatin-Associated Processes, Cell Cycle Control and Tumor Suppression.
The successful candidate is expected to dedicate his time to research and occasional supervision of undergraduate students.

Starting date

2021-01-04

Funding category

Public/private mixed funding

Funding further details

Financing : The annual salary for a PhD student is $25,000 and the HMR research center offers competitive scholarship competition (20K to 30K)for Ph.D students with outstanding academic achievements

Presentation of host institution and host laboratory

Université de Montréal

The goal of our research is to understand the roles of ubiquitin signaling in fundamental DNA-dependent processes most notably transcription regulation and DNA damage/repair. We are using biochemical and molecular biology approaches to investigate the function and mechanism of action of the deubiquitinase and tumor suppressor BAP1, which represents an excellent paradigm for understanding how deubiquitination coordinates DNA-dependent processes and protect against cancer development. The students will acquire a robust experience in state-of-the-art techniques/approaches in biochemistry, molecular oncology and cellular signaling.

Selected publications :

Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1.Daou S, Barbour H, Ahmed O, Masclef L, Baril C, Sen Nkwe N, Tchelougou D, Uriarte M, Bonneil E, Ceccarelli D, Mashtalir N, Tanji M, Masson JY, Thibault P, Sicheri F, Yang H, Carbone M, Therrien M, Affar EB.Nat Commun. 2018 Oct 22;9(1):4385. doi: 10.1038/s41467-018-06854-2.

BAP1 regulates different mechanisms of cell death. Affar EB, Carbone M. Cell Death Dis. 2018 Nov 19;9(12):1151. doi: 10.1038/s41419-018-1206-5.

BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Bononi A, Giorgi C, Patergnani S, Larson D, Verbruggen K, Tanji M, Pellegrini L, Signorato V, Olivetto F, Pastorino S, Nasu M, Napolitano A, Gaudino G, Morris P, Sakamoto G, Ferris LK, Danese A, Raimondi A, Tacchetti C, Kuchay S, Pass HI, Affar EB, Yang H, Pinton P, Carbone M. Nature. 2017 Jun 22;546(7659):549-553.

The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer. Daou S, Hammond-Martel I, Mashtalir N, Barbour H, Gagnon J, Iannantuono NV, Nkwe NS, Motorina A, Pak H, Yu H, Wurtele H, Milot E, Mallette FA, Carbone M, Affar el B .J Biol Chem. 2015 Nov 27;290(48):28643-63.

Undetectable histone O-GlcNAcylation in mammalian cells. Gagnon J, Daou S, Zamorano N, Iannantuono NV, Hammond-Martel I, Mashtalir N, Bonneil E, Wurtele H, Thibault P, Affar el B. Epigenetics. 2015;10(8):677-91.

Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Mashtalir N, Daou S, Barbour H, Sen NN, Gagnon J, Hammond-Martel I, Dar HH, Therrien M, Affar el B. Mol Cell. 2014 May 8;54(3):392-406.

Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S, Barbour H, Corbeil L, Hébert J, Drobetsky E, Masson JY, Di Noia JM, Affar el B. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):285-90.

Roles of ubiquitin signaling in transcription regulation. Hammond-Martel I, Yu H, Affar el B. Cell Signal. 2012 Feb;24(2):410-21.

Crosstalk between O-GlcNAcylation and proteolytic cleavage regulates the host cell factor-1 maturation pathway. Daou S, Mashtalir N, Hammond-Martel I, Pak H, Yu H, Sui G, Vogel JL, Kristie TM, Affar el B. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2747-52.

The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Yu H, Mashtalir N, Daou S, Hammond-Martel I, Ross J, Sui G, Hart GW, Rauscher FJ 3rd, Drobetsky E, Milot E, Shi Y, Affar el B. Mol Cell Biol. 2010 Nov;30(21):5071-85.

 

PhD title

Doctorat en Biochimie et médecine moléculaire

Country where you obtained your PhD

Canada

Institution awarding doctoral degree

Université de Montréal

Graduate school

Candidate's profile

Candidates should have a training in molecular biology or biochemistry or a related discipline (cell biology), have excellent organizational skills, and a strong interest in cell signaling and molecular oncology. A strong emphasis is put towards hard work and scientific discovery.
Bilingual scientific and social environment. Both French and/or English speaking students are encouraged to apply

The PhD duration is usually 4 to 5 years in Canada
 

Application deadline

2020-10-15
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