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Naked Mole-Rat Initiative

The University of Cambridge Naked Mole-Rat Initiative

The naked mole-rat (Heterocephalus glaber) is a mammal with a truly bizarre appearance, looking like an elongated wrinkled sausage with large, protruding teeth. Naked mole-rats live in large underground colonies of approximately 80 animals, which are dominated by a single breeding female, the queen; this social system is highly unusual in mammals, but is similar to that commonly observed in bees and termites and is termed eusocial1.

 

Over the last decade further physiological peculiarities of naked mole-rat physiology have come to light:

Extreme Longevity – naked mole-rats live until 30 years of age, whereas the longevity of similarly sized mice is 2-3 years; moreover, naked mole-rats display sustained good health into old age2

Cancer Resistance – naked mole-rats do not spontaneously develop cancer3 and their cells are resistant to transformation

Insensitivity To Acid As A Noxious Stimulus – naked mole-rats respond normally to mechanical and thermal stimuli, but fail to perceive acid as noxious4

Hypoxia Resistance – naked mole-rat brain tissue can withstand sustained periods of hypoxia and even anoxia5

 

While such phenomena are of great interest there has been little work identifying their causes. In 2014, scientists from the University of Cambridge Department of Pharmacology established the University of Cambridge Naked Mole-Rat Initiative (NMRI), which aims to bring together experts in different scientific areas with the overarching aim being to identify molecular explanations for the highly unusual physiology of this species. The majority of the work carried out by this initiative will be on established NMR cell lines.

An example of previous success in this area comes from a study by Dr Ewan St. John Smith, a founding member of the NMRI, which identified the molecular basis of naked mole-rat acid-insensitivity. It was shown that a variant in the voltage-gated sodium channel NaV1.7 is more greatly inhibited by acid in naked mole-rat pain-sensing neurones (nociceptors) compared to mouse: acid anaesthetises, rather than stimulates, naked mole-rat nociceptors6. This work thus demonstrates the power of comparative physiology: through using standard rodent models the role of voltage-gated sodium channels in the acid-pain pathway had not been demonstrated, but by taking advantage of the naked mole-rat’s natural adaptation to its environment we were able to identify an important function of NaV1.7.

Below you can read about the members of the NMRI, their expertise and current research interests:

Dr Ewan St. John Smith (Pharmacology, Cambridge)

NMRI role: PI

Research Interests: Hypoxia/hypercapnia insensitivity and cancer resistance

Expertise: Electrophysiology, molecular biology, cell culture, immunohistochemistry and behaviour

Podcasts: With Science, The Physiological Society and the Naked Scientist

 

Dr Walid T. Khaled (Pharmacology, Cambridge)

NMRI role: PI

Research Interests: Cancer development and heterogeneity

Expertise: Cancer biology, genetically engineered cancer models and genetic screens

 

Dr Laura Itzhaki (Pharmacology, Cambridge)

NMRI role: PI

Research Interests: Cancer resistance and protein homeostasis

Expertise: Protein folding and stability, cancer therapeutics

 

Dr John Apergis-Schoute (Pharmacology, Cambridge)

NMRI role: PI

Research Interests: Sleep/appetite regulation and hypoxia/hypercapnia insensitivity

Expertise: Behaviour, electrophysiology and immunohistochemistry

 

Dr Pentao Liu (Sanger Institute)

NMRI role: PI

Research Interests: Cancer and mouse development

Expertise: Pluripotent stem cell technology, genetics

 

Dr Kosuke Yusa (Sanger Institute)

NMRI role: PI

Research Interests: Inducible pluripotent stem cells, genetic screens

Expertise: CRISPR screens, genetics

 

1.         Jarvis, J.U. Science 212, 571–3 (1981).

2.         Buffenstein, R. J Comp Physiol B 178, 439–45 (2008).

3.         Delaney, M.A., Nagy, L., Kinsel, M.J. & Treuting, P.M. Vet Pathol 50, 607–621 (2013).

4.         Park, T.J. et al. PLoS Biol 6, e13 (2008).

5.         Larson, J. & Park, T.J. Neurorep 20, 1634–1637 (2009).

6.         Smith, E.S.J. et al. Science 334, 1557 –1560 (2011).