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Understanding host cellular systems that drive an endosymbiotic interaction

Periodic Reporting for period 3 - CELL-in-CELL (Understanding host cellular systems that drive an endosymbiotic interaction)

Reporting period: 2021-07-01 to 2022-12-31

Endosymbiosis is a phenomenon where one cell lives within the cell of a different species. This interaction can be beneficial for both partners i.e. a ‘mutualistic’ relationship. It can also be negative for one or both of the partners. As such, these interactions between cells can be unstable resulting in the interaction breaking down.

Sometimes these interactions evolve so the partners become interdependent and
inseparable. This can lead to the integration of one cell within another to become a critical compartment and component of the host cell. In these cases, the two cells have become one and they now have the same evolutionary destiny.

This process is incredibly important for evolution as it changes the characteristics of the interacting cells and creates novel evolutionary trajectories, allowing radical changes in biology to occur. This process has been fundamental for the evolution of cell complexity and, indeed, played a critical role in the evolution of eukaryotes, a process that eventually led to the evolution of plants, fungi, and animals (including humans). There was probably no more important evolutionary transition in the history of life. In addition, the process of endosymbiosis also played a key role in the spread of photosynthesis, allowing, for example, plants and seaweeds to evolve.

We understand very little about how endosymbiotic interactions can arise, and which cellular mechanisms underpin an interaction to allow such systems to become stable. The aim of this project is to develop an experimental system for identifying the cell biology that controls an endosymbiotic interaction. To do this we focus on a microbe, a single-cell protist, called Paramecium bursaria which can incubate hundreds of photosynthetic green algal microbes within the body of its cell. This is an excellent system for understanding endosymbiotic interactions because the interaction has yet to become an obligate interaction, which means we can experimentally manipulate both partners separately and together. These organisms form an endosymbiotic partnership, exchanging metabolites and providing other functions important for their collective ecology.

The objective of this project is to develop approaches to understand a model endosymbiotic interaction and use these to identify the host cellular systems that can control endosymbiosis. This work will allow us to compare and contrast different endosymbiotic systems and understand how such interactions can evolve. The work will also provide us with the experimental capabilities to modify and perturb these interactions, providing understanding of the cellular and ecological factors that drive these important symbioses.
To understand which cell functions may control the Paramecium bursaria interaction, we have developed a targeted method for perturbing host function. This work will allow the direct study of the host cellular systems that control an endosymbiotic interaction. Furthermore, these experiments can be conducted on a grand scale and, theoretically, every cellular system can be tested in this way. To our knowledge Paramecium bursaria is the first microbial endosymbiosis that is now tractable for reverse genetic manipulation in this way.

As part of this project we have used this approach to conduct a screen of numerous different cellular systems. We believe our project will be viewed as successful if we can identify one or more of the cellular systems which control the endosymbiotic interaction, and then demonstrate that modification/perturbation of such a system leads to a change in the endosymbiotic interaction dynamic and outcome.

We have begun the screening process. So far, our work has identified:

i) how the host can control the endosymbiont through a specific metabolic interaction

ii) how the host can recognise the endosymbiont by detecting its cellular coating

iii) how the endosymbiont can generate a cost - a punishment - to the host for destroying the endosymbionts.

These factors are all important for the stability of the endosymbiotic interactions. Furthermore, they show we can now manipulate the interaction in several different ways, opening up the opportunity to conduct a combination of cell biological and ecological interaction-based experiments in order to fully understand the dynamics of an endosymbiotic cellular interaction both from the perspective of cell function and evolutionary ecology.
We believe we have achieved key progress beyond the state of the art in two ways:

i) We have developed a targeted method for perturbing host function so we can identify host cell systems that control the interaction. To our knowledge, Paramecium bursaria is the first microbial endosymbiosis that is now tractable for reverse genetic manipulation on a grand scale, allowing the direct study of any host-encoded cellular systems that control an endosymbiotic interaction.

ii) We have identified three different cellular systems: metabolic exchange, cellular recognition, and punishment, which we can manipulate to alter the outcome of the interaction in different ways.

Collectively our work has opened up the opportunity to conduct a combination of cell biological and ecological interaction-based experiments in order to fully understand the dynamics of an endosymbiotic cellular interaction.

In the next period of the project, we will expand our screening approach, confirm the subcellular location for components of the systems we have identified (and any additional ones we identify), and develop new approaches to explore the ecological and cellular dynamics of an endosymbiotic interaction.
Fluorescent image of photosynthetic algae inside Paramecium bursaria