ERA Chair - RNA and Immunity - Mary O´Connell
CEITEC MU CEITEC MU
ERA Chair - RNA and Immunity - Mary O´Connell

PhD Topics

Mary O'Connell Research Group studies protein called ADARs and is known worldwide for its unique expertise in this field. PhD students in this group have a unique opportunity to work in a multicultural research group under experienced native English speaking supervisors, professor Mary O´Connell and doctor Liam Keegan. Students receive comprehensive support from the beginning of their studies and start their scientific career as confident and globally competitive researchers. Read a testimonial of recent PhD graduate HERE

 

1. Using Drosophila as a model to study the epitranscriptome and how it regulates innate immunity

Supervisor: prof. Mary Anne O'Connell

Annotation: 

The ADAR enzymes deaminate adenosine bases in dsRNA in pre-mRNAs to inosine, which can be read as guanosine by the translational machinery, recoding individual codons in some ADAR-edited transcripts. The conversion of adenosine to inosine in endogenous dsRNA also helps the cell distinguish self from foreign/viral/pathogenic dsRNA. This is essential as without it, unedited endogenous dsRNA binds to cellular dsRNA sensors and activates innate immune responses (doi: 10.1016/j.celrep.2014.10.041). In Drosophila, many important neuronal transcripts are edited by the single Adar. The Adar mutant is partially viable and suffers ataxia as well as synaptic defects and age-related neurodegeneration (doi: 10.1186/s12915-020-0747-0). Unexpectedly the Drosophila mutant also has aberrant innate immune induction and antiviral response activation (doi: 10.1186/s12915-020-0747-0). The PhD student will study Adar’s role in innate immunity in Drosophila and also in Drosophila S2 cell lines.

Recommended literature:

  • K. Sinigaglia et al. ADAR RNA editing in innate immune response phasing, in circadian clocksand in sleep Biochim Biophys Acta Gene Regul Mech 2019 1862(3):356-369
  • M. A. O'Connell, N. M. Mannion, L. P. Keegan, The Epitranscriptome and Innate Immunity. PLoS Genet 11, e1005687 (2015).
  • A. Khan et al A Membrane and synaptic defects leading to neurodegeneration in Adar mutant Drosophila are rescued by increased autophagy. K BMC Biol. 2020 Feb 14;18(1):15.
  • P. Deng Adar RNA editing-dependent and -independent effects are required for brain and innate immune functions in Drosophila.  Nat Commun. 2020 Mar 27;11(1):1580.

Funding:
This PhD student will be funded as part of a Marie Skłodowska-Curie Innovative Training Networks (MSCA-ITN) on Epitranscriptomics (ROPES) which is funded by the European Commission. The candidate will also benefit from this training program which includes secondments abroad to work in other research groups within the consortium, a variety of training modules, as well as courses on transferable skills and active participation in workshops and conferences. More information about the MSCA-ITN ROPES project can be found HERE

Requirements on candidates:

We are looking for applicants who are motivated and creative. Experience in research with Drosophila is desired but not essential. The applicant must have good English language skills – both spoken and written. The PhD candidate must have a Masters degree. Before applying all applicants should read the eligibility criteria for the MSCA-ITN PhD program HERE. 

Keywords: RNA modification, epitranscriptome, ADAR, innate immunity, Drosophila

Apply HERE!

 

2. Investigating epitranscriptomics in a mouse model, with particular focus on the ADAR enzymes

Supervisor: prof. Mary Anne O'Connell

Annotation: 

The ADAR enzymes deaminate adenosine bases in dsRNA in pre-mRNAs to inosine, which can be read as guanosine by the translational machinery, recoding individual codons in some ADAR-edited transcripts. In vertebrates, one of the most critical recoding events maintains the calcium impermeability of GluA2 subunit-containing AMPA receptors and this is catalyzed by Adar2. Adenosine to inosine conversion in endogenous dsRNA also helps the cell distinguish self from foreign/viral/pathogenic dsRNA. This is essential as without it, unedited endogenous dsRNA binds to cellular dsRNA sensors and activates innate immune responses (doi: 10.1016/j.celrep.2014.10.041) and Adar1 required for this. A PhD student will investigate these roles of Adar1 and Adar2 further using mouse mutants and cell cultures which are available within the group.

Recommended literature:

  • M. A. O'Connell, N. M. Mannion, L. P. Keegan, The Epitranscriptome and Innate Immunity. PLoS Genet 11, e1005687 (2015).
  • N. M. Mannion et al., The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Rep 9, 1482-1494 (2014)
  •  G. I. Rice et al., Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nature genetics 44, 1243-1248 (2012)
  •  K. Sinigaglia et al. ADAR RNA editing in innate immune response phasing, in circadian clocksand in sleep Biochim Biophys Acta Gene Regul Mech 2019 1862(3):356-369

Funding:
GA ČR EXPRO

Requirements on candidates:

We are looking for applicants who are motivated and creative. Experience in research with mice is desired but not essential. The applicant must have good English language skills – both spoken and written. The PhD candidate must have a Masters degree. 

Keywords: RNA modification, epitranscriptome, ADAR, innate immunity, Glutamate receptor

 

Apply HERE!