Investigating the long-term effects of chronic radiation exposure on immunity

Overview

Despite decades of research into radiation effects on wildlife, controversy remains concerning the dose rate at which significant impacts occur for different types of organisms. Recent studies around sites of reactor accidents Chernobyl (1986) and Fukushima (2011) have indicated potential biological effects in the field which are at odds with our expectations from laboratory studies. Furthermore, in humans exposed to radiation from the Mayak Nuclear Facility, the cellular impact of chronic radiation, as observed in increase somatic mutations, frequency of micronuclei, and nitric oxide and apoptosis in peripheral blood lymphocytes, seems to affect ‘radiosensitive humans’ but not every individual. Given there is increasing interest in understanding how and why sensitivity to radiation exposure varies between individuals, there is a need to better understand the effects of radiation not only on whole organisms, but also on cellular functions and to link the impact of exposure to a distinct physiological effect.

Within this project we will expose two well characterised model organisms, namely the waxmoth larvae (Galleria mellonella) and the freshwater protozoa Tetrahymena thermophila to a constant source of radiation, in our radiation facility, which mimics the radiation conditions in contaminated environments. Next, we will compare the impact of chronic radiation on these organisms through the study of a range of biochemical and immunological responses, such as gene/protein expression, melanisation, phagocytosis, reactive oxygen species (ROS) production/accumulation, etc.

This project fits within the remit of the Grand Challenges outlined by the Industrial Strategy Policy paper on Clean Growth. As the global economy moves into low carbon technologies, which may include nuclear energy, it is crucial that we have a better understanding of how cells are affected by chronic low dose radiation. This will ultimately help with the current public debate as well as inform government policy into the use of nuclear as a source of energy.

Methodology

The project will utilise the specialist experimental facilities at the University of Stirling for radiation exposure experiments. The student will expose the model organisms to a constant, low-dose radiation for fixed periods of time. S/he will assess the immunity of these model organisms by challenging them with bacterial and/or fungal pathogens. S/he will also study genotoxic effects and oxidative stress, via fluorescence microscopy, flow cytometry or plate readers. Furthermore, regulation of specific genes will be determined by transcriptomics using RNA extracted from either the hemocytes (G. mellonella) or entire cells (T. thermophila). Any interesting up- or down- regulated genes will be analysed by western blots.

Project Timeline

Year 1

Understanding the invertebrate immune system;

Conduct a literature review and design an appropriate research strategy for work within the radiation facility and laboratory (biochemistry/cell biology) studies;

Culturing and/or maintaining model organisms in control and radioactive conditions and track their life cycles.

Undergo training in genomics & RNA-seq Data Analysis.

Attend and present at one local conference.

Year 2

Implement the laboratory programmes by introducing the model organisms to constant low-dose radiation & determine the cellular impact of radiation on them.

Attend and present at one local conference.

Year 3

Expose the model organisms to constant low-dose radiation & analyse their transcriptome to identify variation in gene regulation.

Attend and present at one local and one overseas conference.

Year 3.5

Thesis finalisation and paper writing (although it is anticipated that these activities will be ongoing throughout the PhD).

Training
& Skills

The analytical techniques required for this study are already established at the University of Stirling and include: SDS-PAGE, western blotting, microbiological / biochemical assays, using microscopy & plate readers. S/he will receive training in experimental design, data analysis, and radiological protection related to the project work. S/he will attend classes on Effective Research, Scientific Writing, Statistics for Environmental Evaluation (and use of R), Presentation Skills, and Radiological Environmental Protection. S/he will attend 2 external courses run by Edinburgh Genomics in Linux for Genomics & RNA-seq Data Analysis.

The student will also benefit from wider interaction within research groups at Stirling and CEH Lancaster. We will establish regular meetings via Skype between CEH and Stirling to allow discussions on the student’s work. S/he will be expected to present the results of their research annually at the BES student symposium and to attend the annual UK COGER meetings which have an emphasis on encouraging students to present their work. The student will also be expected to present their work at one conference. The student will have the opportunity to interact with wider student networks (and training opportunities) though the European Radioecology ALLIANCE.

References & further reading

Beresford, N.A., Copplestone, D. 2011. Effects of Ionizing Radiation on Wildlife: What Knowledge Have We Gained Between the Chernobyl and Fukushima Accidents? Integer. Environ. Ass. Manag., 7, 371-37.

Copplestone, D., Beresford, N.A., Howard, B.J. 2010. EDITORIAL: Protection of the Environment from Ionising Radiation: developing criteria and evaluating approaches for use in regulation. J. Radiol. Prot., 30, 191-194.

Veremeyeva G, Akushevich I, Pochukhailova T, Blinova E, Varfolomeyeva T, Ploshchanskaya O, Khudyakova O, Vozilova A, Kozionova O, Akleyev A. 2010. Long-term cellular effects in humans chronically exposed to ionizing radiation. Health Phys. 99:337-346.

Further Information

Jenson Lim +44 (0) 1786 467821, Email: jenson.lim@stir.ac.uk
David Copplestone +44 (0)1786 467852, Email: david.copplestone@stir.ac.uk
Nick Beresford +44 (0)1524 595856, Email: nab@ceh.ac.uk

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