PhD studentship – The role of the microbiome and circulating endothelial cells in CRGV

The Alabama Rot Research Fund (ARRF) is sponsoring in 2020 a three year PhD studentship – ‘The role of the microbiome and circulating endothelial cells in the pathobiology of cutaneous renal glomerular vasculopathy (CRGV)’.

‘Initial findings have shown that the gut microflora (bacterial/bug population) of dogs affected by CRGV differs significantly from healthy dogs’.

Aim of the research project

‘This PhD studentship aims to characterise the gut microflora, blood changes and other factors associated with the disease, in order to try and determine the cause, and hopefully, in time, improve the ability to diagnose and treat the disease.’

Scientific summary

‘Gut microbiome studies – To gain an understanding of the gut microflora changes associated with CRGV and identify bacterial species (or changes in abundance and diversity) that may be associated with the disease.’

  • Next-generation sequencing allows all microorganisms in the gut to be identified using DNA sequencing
  • faecal samples will be collected from healthy (50) and affected dogs (50)

‘Body fluid metabolite studies – To determine any metabolic changes in body fluids that may be associated with CRGV and that could be used as diagnostic markers.’

  • Metabolic profiling (metabonomics/metabolomics) measures low-molecular-weight compounds in a biological sample, capturing the metabolic profile or phenotype.
  • NMR will produce metabolic signatures and identify correlations between affected dogs and controls genotype.

Clinical pathology – To determine if the presence of CEC’s and or increased ANCA can be used as predictors of CRGV.’

  • The student will review the literature on vasculopathy in humans to gain ideas and insights that might be applicable to CRGV.
  • Whilst humans are not affected by CRGV specifically, they do suffer from renal glomerular vasculitis (RGV), which bears some similarity with the renal pathology seen in CRGV.
  • A common cause of human RGV is the production of anti-neutrophil cytoplasmic (auto) antibody (ANCA), often secondary to viral or bacterial infections. 
  • Although the cause of canine CRGV is unknown, one suggestion is that it is caused by a toxin produced by the bacterium Aeromonas hydrophila following environmental exposure to the organism. A. hydrophila produces a cytolytic endotoxin that promotes chemotaxis of neutrophils.
  • One hypothesis we have is that the pathology of CRGV is driven by ANCA, secondary to an infection, such as with A. hydrophila.
  • Circulating endothelial cells (CECs) are a reliable marker of disease activity in a variety of vascular disorders. Damage to microvascular endothelial cells is a hallmark of thrombotic microangiopathy. Therefore, we will investigate whether circulating endothelial cells predict either development of acute kidney injury or outcome in CRGV patients.
  • The human literature suggests that elevated numbers of CECs may be a reliable prognostic marker for vascular diseases, but this has not been tested fully in dogs.
  • In this PhD project, we shall isolate CECs from dogs and compare the control and affected dogs.

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