Prof Uri Frank

Professor of Developmental Biology
Wellcome Trust Investigator

Research interests

  • Developmental biology
  • Stem cell biology
  • Regeneration biology

Research overview

During development, uncommitted embryonic cells become progressively more specialized and less flexible. This process is based on cell type specific epigenetic modifications, particularly alterations of the chromatin landscape, which reinforce specific gene expression patterns that drive cell identity and maintain it life-long.

A wild type colony of Hydractinia echinata

Loss of cellular plasticity, i.e. having a stable fate, is essential to sustain complex structures in higher animals and to prevent malignancy. This stability, however, comes at a price because stably differentiated cells have decreased regenerative potential, being no longer able to give rise to all tissues.

Some basal animals have adopted a different strategy during their evolution: they keep a simpler body structure, allowing them to maintain cellular plasticity life long. Because all extant animals are derived from a common ancestor and use very similar genetic toolkits, one may hypothesize that what makes the difference is merely alternative usage of the same genes. Hence, studying basal, flexible animals provides the opportunity to gain insight into topics such as cellular differentiation and stemness in a comparative fashion.

Galway Anatomy Department 9000 8.0 75 Imaging small enclosed outgrowth 3 XpixCal=96.906 YpixCal=96.906 Unit=micron ##fv3

A stinging cell (nematocyte). Image by Cathriona Millane

Our interest in developmental biology is broad, but for now we primarily focus on a number of topics such as acquisition of neural fate; maintenance of stemness, germ cell biology, and the chromatin biology underlying these processes.

We use the highly regenerative cnidarian, Hydractinia echinata, as a model organism in the lab. The animal is a relative of corals, sea anemones and jellyfish. It is sedentary, small and translucent, perfect for live imagining. Genetic manipulation can be easily achieved. Hydractinia reproduces sexually and clonally, can regenerate any lost body part, and show no signs of aging under laboratory conditions.

This allows for us to study a host of developmental processes relating to embryonic development, tissue homeostasis and regeneration.

 

Selected publications

  • Sanders SM, Ma Z, Hughes JM, Riscoe BM, Gibson GA, Watson AM, Flici H, Frank
    U, Schnitzler CE, Baxevanis AD, Nicotra ML (2018). CRISPR/Cas9-mediated gene knockin in
    the hydroid Hydractinia symbiolongicarpus. BMC Genomics. Sep 3;19(1):649.
    doi: 10.1186/s12864-018-5032-z. PubMed PMID: 30176818; PubMed Central PMCID:
    PMC6122657.
  • Flici H, Frank U (2018). Inhibition of SoxB2 or HDACs suppresses Hydractinia head
    regeneration by affecting blastema formation. Commun Integr Biol. Apr
    3;11(2):1-5. doi: 10.1080/19420889.2018.1450032. eCollection 2018. PubMed PMID:
    30083285; PubMed Central PMCID: PMC6067865.
  • Gahan JM, Schnitzler CE, DuBuc TQ, Doonan LB, Kanska J, Gornik SG, Barreira S, Thompson K, Schiffer P, Baxevanis AD, Frank U (2017). Functional studies on the role of Notch signaling in Hydractinia development. Dev Biol 428(1): 224-231.
  • Flici H, Schnitzler CE, Millane RC, Govinden G, Houlihan A, Boomkamp SD, Shen S, Baxevanis AD, Frank U (2017). An evolutionarily conserved SoxB-Hdac2 crosstalk regulates neurogenesis in a cnidarian. Cell Reports 18: 1395-1409.
  • Bradshaw B, Thompson K, Frank U (2015). Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata. Elife 4: e05506
  • Kanska J, Frank U (2013). New roles for Nanos in neural cell fate determination revealed by studies in a cnidarian. J Cell Sci 126: 3192-3203