Understanding how cells make an organism: cooperation and conflict between cells in planarians

Key Questions

This project asks how within-organism selection affects organismal function: does a genetically heterogeneous animal suffer because of internal conflicts? Or does increased heterogeneity potentially provide benefits? 

Background

Millions of cells cooperate to produce complex multicellular organisms. When building a complex body, most cells usually form sterile somatic cells that give up their ability to reproduce to instead help germ cells reproduce. This is a highly altruistic act, and it is thought that all cells within the body need to be clonally related for this cooperation to be stable. A number of ‘basal’ animal lineages, however, reproduce in ways that potentially allow genetic diversity to persist, and therefore potentially enable within organism conflict and selection—they challenge our understanding of multicellularity.

Aims of the Project

We use planarian flatworms as a model system. The planarians are remarkable: they comprise approximately 10% pluripotent stem cells, they are potentially immortal, they can regenerate whole worms from even the smallest tissue fragments, and they can reproduce by simply ripping themselves in two. We use these properties to manipulate the levels of genetic diversity, and therefore the strength of selection, within individual worms to assess the potential costs and benefits of within organism heterogeneity. In this project, we challenge these worms with a generalist pathogen and ask whether chimeric worms with high diversity are better able to fight off infection. 

Project Description

Millions of cells cooperate to produce complex multicellular organisms. When building a complex body, most cells usually form sterile somatic cells that give up their ability to reproduce to instead help germ cells reproduce. This is a highly altruistic act, and it is thought that all cells within the body need to be clonally related for this cooperation to be stable. A number of ‘basal’ animal lineages, however, reproduce in ways that potentially allow genetic diversity to persist, and therefore potentially enable within organism conflict and selection—they challenge our understanding of multicellularity.  

This project asks how within-organism selection affects organismal function: does a genetically heterogeneous animal suffer because of internal conflicts? Or does increased heterogeneity potentially provide benefits? 

We use planarian flatworms as a model system. The planarians are remarkable: they comprise approximately 10% pluripotent stem cells, they are potentially immortal, they can regenerate whole worms from even the smallest tissue fragments, and they can reproduce by simply ripping themselves in two. We use these properties to manipulate the levels of genetic diversity, and therefore the strength of selection, within individual worms to assess the potential costs and benefits of within organism heterogeneity. In this project, we challenge these worms with a generalist pathogen and ask whether chimeric worms with high diversity are better able to fight off infection. 

This question has direct parallels with the evolution of eusocial insect colonies. There, queens that establish colonies were ancestrally monogamous, but in many lineages (eg. honeybees, leaf-cutter ants, army ants), queens now mate with many males before founding a colony. This leads to decreased relatedness within a colony that could create conflict, but must lead to benefits for increased mating frequency to have repeatedly been selected for. It is thought increased colony resistance to pathogens may be one such benefit.  

We will create chimeric planarian individuals, and challenge them with a generalist pathogen. We will test how chimeric worms cope with this challenge compared to typical worms by:  

• Generating survival curves; 

• Generating growth/ de-growth curves; 

• Estimating Regenerative ability; 

• Potentially estimating frequency of clones within an organism using high-throughput sequencing. 

This project offers an opportunity to develop animal handling skills, microbiology, and potentially molecular techniques. It will use elements of computer vision, including some basic machine learning software. 

Methods to be used

We will create chimeric planarian individuals, and challenge them with a generalist pathogen. We will test how chimeric worms cope with this challenge compared to typical worms by:  

• Generating survival curves; 

• Generating growth/ de-growth curves; 

• Estimating Regenerative ability; 

• Potentially estimating frequency of clones within an organism using high-throughput sequencing. 

Specialised skills required

This project offers an opportunity to develop animal handling skills, microbiology, and potentially molecular techniques. It will use elements of computer vision, including some basic machine learning software.  

Please contact Ashleigh Griffin on Ashleigh.griffin@zoo.ox.ac.uk   if you are interested in this project