Wellcome Trust Centre For Mitochondrial Research

Shreya Ayyub

Biography

I am a Postdoctoral Research Associate working in the laboratories of Professor Robert Lightowlers and Professor Zofia Chrzanowska-Lightowlers. I obtained my BSc degree with a double major in Life Sciences and Biochemistry from St. Xavier’s College, Mumbai. I carried out my MSc, PhD and postdoctoral work in the field of bacterial translation at the Indian Institute of Science, Bangalore. During my PhD, I studied the regulation of translation initiation using E. coli as a model system to characterise bacterial and mitochondrial translation factors, which triggered my interest in studying mitochondrial protein synthesis in humans. My current work at the centre deals with the characterisation of human mitochondrial release factors.

Research Project

Understanding the roles of uncharacterised release factors in human mitochondrial translation and ribosome rescue

Principal Investigators: Prof. Robert Lightowlers and Prof. Zofia Chrzanowska-Lightowlers

Project Details

Although, the clinical consequences of mitochondrial dysfunction have been extensively characterised, there is a surprisingly rudimentary understanding of quality control mechanisms in the human mitochondrial translation system. In order to understand the molecular pathogenesis of many of these disorders, we need to identify essential factors that monitor and maintain accurate protein synthesis. Of the four human mitochondrial release factors (RFs), only mtRF1a is required to terminate translation of the 13 genes encoded by the mitochondrial genome. Interestingly, depletion of any of the remaining three (mtRF1, ICT1 and C12orf65) causes loss of cell viability, and mutations in C12orf65 are responsible for mitochondrial disease. I aim to use three approaches: generation and characterisation of relevant CRISPR/Cas9 gene knockouts, cryo-electron microscopy to elucidate the RF/mitoribosome interaction, and use of a cell line that has a defect causing stalled mitoribosomes, to understand the regulation of translation termination and ribosome rescue by mtRF1 and C12orf65.

Email: shreya.ayyub@ncl.ac.uk

External links: https://scholar.google.co.uk/citations?user=EDTAXFkAAAAJ&hl=en 

Publications:

  1. Ashwin Govindan, Shreya Ahana Ayyub and Umesh Varshney. Sustenance of Escherichia coli on a single tRNAMet. (Accepted for publication in Nucleic Acids Research on 11/09/2018)
  2. Shreya Ahana Ayyub, Kuldeep Lahry, Divya Dobriyal, Sanjay Mondal and Umesh Varshney. (2018) Antimicrobial activity of fusidic acid in Escherichia coli is dependent on the relative levels of ribosome recycling factor (RRF) and elongation factor G (EFG); FEMS Microbiology Letters, Volume 365, Issue, fny133, https://doi.org/10.1093/femsle/fny133
  3. Shreya Ahana Ayyub, Divya Dobriyal, Riyaz Ahmad Shah, Kuldeep Lahry, Souvik Bhattacharyya, Madhumita Bhattacharyya, Saikat Chakrabarti and Umesh Varshney. (2018) Coevolution of the translational machinery optimizes initiation with unusual initiator tRNAs and initiation codons in mycoplasmas; RNA Biology, 15:1, 70-80, DOI: 10.1080/15476286.2017.1377879
  4. Shreya Ahana Ayyub, S.L. Aswathy, Divya Dobriyal, Srinivas Aluri, Linda L. Spremulli and Umesh Varshney. (2017) Fidelity of translation in the presence of mammalian mitochondrial initiation factor 3; Mitochondrion. Aug 10. pii: S1567-7249(17)30141-1
  5. Shreya Ahana Ayyub, Divya Dobriyal and Umesh Varshney. (2017) Contributions of the N-terminal and C-terminal domains of initiation factor 3 towards its functions in the fidelity of initiation and anti-association of the ribosomal subunits. J Bacteriol. Mar 20. pii: JB.00051-17
  6. Anusha Krishnan, Kanchan Anand Joshi, Ambily Abraham, Shreya Ayyub, Mohini Lahiry, Ritwika Mukherjee, Saniya Milind Javadekar, Vignesh Narayan and Renee M Borges. (2014) Finding hidden females in a crowd: Mate recognition in fig wasps; Acta Oecologica, Vol. 57, P. 80–87.