PhD Studentship: Does Sex Really Matter? Quantifying the Importance of Sexdisaggregated Analysis for Improving Experimental Reproducibility in an Experimental Fish Model. BBSRC SWBio DTP PhD Studentship 2023 Entry. PhD in Biosciences.

The BBSRC -funded South West Biosciences Doctoral Training Partnership (SWBio DTP ) involves a partnership of world-renown universities, research institutes and industry across the South West and Wales.

This partnership represents a distinctive group of bioscientists, with established international, national and regional networks, and widely recognised research excellence. 

We aim to provide students with outstanding interdisciplinary research training within the following themes, underpinned by transformative technologies: 

Advancing the frontiers of biosciences discovery

Biosciences for sustainable agriculture and food

Biosciences for an integrated understanding of health  

These are growth areas of the biosciences and for which there will be considerable future demand. 

The Award:

This project is one of a number that are in competition for funding from the South West Biosciences Doctoral Training Partnership (SWBio DTP). 

Project Description

Sex as an experimental factor is largely overlooked within the biological sciences, particularly outside a human biomedical model (Ellis et al 2017). 

Nonetheless, a growing body of research has demonstrated significant, and often unexpected, impacts across a broad suite of behavioural, physiological and molecular systems within experimental organisms. When unaccounted for, sex based differences lead to an increase in unexplained experimental variance, a lack of reproducibility and the increased likelihood of misinterpretation of experimental outcomes (Tannenbaum et al 2019). Sex analysis is thus key for improving the accuracy and robustness of scientific research. Zebrafish represent the main experimental model for fish research globally, and constitute the second most used vertebrate species in research. 

Nonetheless, major challenges exist in the use of this species as a model due to the impact of environment on sex determination, as well as the difficulty in sexing fish prior to experimentation. This often results in a failure to disaggregate or report sex in zebrafish experiments, or where tested a posteriori, leads to an increase in experimental animals used. 

Results from other non-human vertebrate models have highlighted large significant differences between males and females with respect to responses to drugs, mechanisms in pain reception and stress induced gene regulation (Labonte et al 2017; Sorge et al 2015; Tannenbaum and Day 2017), whilst wider research has shown sex based differences impact behavioural, physiological, immunological, molecular and neurotoxicological functions. With temperature (and other key environmental factors) significantly influencing zebrafish sex, subtle variations in conditions across facilities can lead to unintended sex ratio bias. When left uncorrected, this significantly increases experimental variability, ultimately increasing animal numbers and reducing experimental reproducibility. 

A key example of this is the use of zebrafish in regulatory testing of contaminants, particularly the OECD234 sex determination assay. Inability to sex individuals prior to experimentation, and thus ensure a balanced sex ratio, often results in a requirement of 800 individuals being tested to ensure sufficient numbers of males and females are assessed in control conditions. Use of a genetically determined species, where sex can be ascertained prior to experimentation (via non-invasive PCR assays), as is the case with medaka, could significantly reduce experimental animals used. 

This project aims to quantify the importance of disaggregating sex in experimental research, and proposes to do so using a species in which sex is genetically determined, and thus stable – the medaka (Oryzias latipes).