David C. Queller - US grants

The PIs will investigate recognition of self and kin in an amoeba, Dictyostelium discoideum. These single-celled amoebas come together to form a multicellular fruiting body, but they do so primarily with members of their own genetically identical clone, rejecting genetically different clones. The researchers will study the costs and benefits of recognition, particularly how it protects against exploitation by foreign clones. They will also investigate whether recognition simply involves avoidance of other clones, or whether it also leads to attacks on the foreign clone, analogous to tissue rejection. Finally, they will also identify the genes that cause recognition.

Recognition systems are vital to life. For example, self-recognition is what allows humans to detect and attack pathogens, and it also plays a critical role in organ transplantation. D. discoideum is a good single-celled lab organism, has a sequenced genome, shares many genes with humans, and has many molecular and genetic techniques developed for it. Therefore these investigations will result in a valuable model system for the study of recognition, leading to insights into general questions of how recognition works and evolves, that are not easily addressed in other organisms.

This work will explore two fundamental questions about multicellularity. First, are the early stages of development necessarily the hardest to change? This seems true in animals, but the project will test whether this pattern is general, using genomic data in a very different multicellular system, a social amoeba in which is normally a single-celled eukaryote, but upon starvation aggregates and differentiates into a structure with reproductive spores and sterile stalk cells. The second question is, how do multicellular organisms protect themselves from mutant cell lineages that replicate too fast? The project will use the novel strategy of constructing pseudo-organisms with artificial life cycles. By allowing these to evolve and monitoring cellular cooperation, the project will isolate factors that maintain multicellularity.


The most advanced organisms on earth, including people, animals, and plants, are all multicellular. Yet there is much that we do not understand about how and why multicellularity works. By focusing an unusual developmental system, the project will test how events at one time or place in development affect and constrain events at other times and places. They will also conduct the first rigorous tests of what life cycles protect against conflict among cells - cancer being a prominent example. The project will contribute to scientific training and will reach out to the public via websites, science cafes, and events for K-12 students.

Kinship is a crucial element in many kinds of cooperation. In order for individuals to cooperate with their kin they must identify their relatives somehow. This can happen through the structure of the environment, or through active recognition processes. Recognition and cooperation can benefit many kinds of organisms. Some of these organisms include microbes where cooperation can actually harm the animal hosts, so understanding kin recognition and cooperation in microbes can have important implications for human welfare.

The investigators will study kin structure and recognition in a social amoeba that has a solitary stage where it eats bacteria and a social stage where it aggregates into a multi-cellular collective that moves and produces spores. They have found that this amoeba can distinguish between related and unrelated individuals and these amoebae use this ability to avoid unrelated amoebae and to protect certain kinds of bacteria. The investigators will test different mechanisms for recognizing relatives in this system. They will document the growth patterns of the amoebae as they prey upon bacteria. They will examine genes for recognition and they will consider the role of dispersal distance in recognition. Furthermore the investigators will explore the mechanisms through which these amoebae exploit the toxicity of bacteria. Taken together, this research has great potential to promote our understanding of the interactions between microbes; which in turn will contribute to our understanding of how microbes directly affect humans and the environment in which we live. The project will contribute to the scientific training of undergraduate and graduate students and will reach out to the public via websites, Wikipedia entries, and events for K-12 students.

Members of different species sometimes associate and adapt to each other. Sometimes the associations are mutually beneficial, as in many of the bacteria associated with the human gut. In this work, the investigators will explore the mostly beneficial interactions in a much simpler system where several bacterial species are carried in the gut of an amoeba. The bacteria gain by being transported to new localities in amoeba spores while the amoeba gains by being able to seed out populations of food bacteria in new areas. The result is a sort of primitive farming. The investigators will first explore how selection works on this system using experiments to test new theory that could also be applied to more complex systems. Second, they will explore how the partnerships are formed. Are the partners attracted to each other and are particularly good food bacteria favored? Finally, the investigators will determine many of the amoeba and bacterial genes that control this interaction, exploiting the fact that both partners can be genetically manipulated. The students and post-doctoral individuals in this project will gain valuable training in important areas like genomics. The investigators will also impact high school students through on-campus workshops, undergrads and grads via a blog on being an academic, and the local community via an innovative science booth at the Ferguson farmer's market.

The social amoeba Dictyostelium discoideum and two clades of Burkholderia bacteria engage in a remarkable microbiome-like symbiosis. The Burkholderia gain dispersal inside amoeba spores and also induce carriage of food bacteria that are released after spore dispersal to seed new food crops for the amoebas. This model system for symbiosis exploits short lifespans, small genomes, genetically manipulability, and other advantages. The PIs will use a new theoretical framework to estimate components of selection for both partners (Aim 1). This framework draws on analogies with kin selection theory and promises to be similarly useful. Second, they will explore partner association, testing how Burkholderia and Dictyostelium find each other, whether they succeed at choosing beneficial partners, and whether there is preferential association with beneficial food bacteria. Finally, they will discover many of the genes involved in the symbiosis and how they have evolved (Aim 3). Insertional mutant libraries of both partners will be constructed, put through various selection regimes, and sequenced to determine frequency changes that will identify relevant genes.