Prof Brian McStay
Professor in Biochemistry
Wellcome Investigator
EMBO Member
brian.mcstay@universityofgalway.ie


Research interests

  • Human acrocentric chromosomes
  • Chromosomal context of human NORs
  • Nucleolar formation and organisation
  • Genome stability of rDNA arrays

Research overview

Nucleoli, sites of ribosome biogenesis and the largest structures in the human nucleus, form around nucleolar organiser regions (NORs) located on the short or p-arms of five different chromosomes referred to as acrocentric chromosomes (see McStay, 2023). NORs comprise ribosomal genes (rDNA) arrays coding for the major RNA components of ribosomes.

Ribosomal gene arrays are located on the p-arms of each of the five human acrocentric chromosomes. Distal and proximal junctions abut rDNA arrays on their telomeric and centromeric ends [Source]

How multiple acrocentric p-arms gather together to form a nucleolus and how NORs partition within nucleoli are important but unanswered questions. Progress has been hampered by the inability to distinguish acrocentric p-arms from each other due to their shared DNA-sequences (see Van Sluis et al, 2019 and Van Sluis et al, 2020).

A reverse genetics strategy for studying acrocentric p-arms. Precision chromosome engineering is performed on single acrocentric chromosomes held within mono-chromosomal somatic cell hybrids. The engineered chromosomes are then transferred into human cells to assess the functional impact [Source]

To circumvent this, we have developed powerful chromosome-engineering approaches on single human chromosomes held in mono-chromosomal somatic cell hybrids.

A model for nucleolar organisation in normal growth conditions and under nucleolar stresses [Source]

These custom engineered chromosomes can then be reintroduced into human cells to test function in nucleolar formation (see Mangan & McStay, 2021).

Using this transformative technology and Wellcome Investigator funding, we are currently addressing the following aims:

  1. Characterise chromosomal requirements for the formation of large multivalent nucleoli
  2. Identify factor(s) constraining NOR-territories (see Mangan & McStay, 2021)
  3. Explore cellular responses to rDNA DSBs using genome-edited human NORs (see Van Sluis & McStay, 2015)

Keywords

Human acrocentric chromosomes, nucleolar organiser regions (NORs), nucleolus, ribosomal genes (rDNA), rDNA genome stability.

Research Techniques

  • Genome Editing
  • Precision Chromosome Engineering
  • Microscopy
  • Next Generation Sequencing

Lab Members

  • Dr Hazel Mangan (PD)
  • Dr Emiliano Perdomo (PD)
  • Krystyna Giemza (PhD)
  • Maria O’Keefe (PhD)
  • Tom Durkin (RA & MSc)

Selected publications

Most Recent Publications

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Get in Touch!

brian.mcstay@universityofgalway.ie