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Robert Noble

Publications and source records attributed to Robert Noble.

2 recordsLinked to original sources

Enhancing synergy of CAR T cell therapy and oncolytic virus therapy for pancreatic cancer.

The poor immunogenicity of pancreatic tumors makes them particularly difficult to treat. Standard chemotherapies and single agent immunotherapies have had notoriously little success in this arena. Oncolytic virus therapy has the potential to enhance the penetration of immunotherapeutically-delivered CAR T cells into the tumor and improve treatment outcomes. We evaluate this potential by combining two different mathematical approaches: an ordinary differential equation model to simulate population level tumor response to cytotoxic activity of T cells, coupled with an agent-based model to simulate the enhancement of CAR T cell penetration by oncolytic virus therapy.

Cancer Biology

Antibiotic Stress Selects against Cooperation in a Pathogenic Bacterium

Ecological antagonisms such as predation, parasitism, competition, and abiotic environmental stress play key roles in shaping population biology, in particular by inducing stress responses and selecting for tolerant or resistant phenotypes. Little is known, however, about their impact on social traits, such as the production of public goods. Evolutionary trade-off theory predicts that adaptation to stresses should lessen investments in costly helping behaviours when cooperation does not increase resistance or tolerance, but support for this prediction is scarce. We employed theory and experiments to investigate how ecological antagonism influences social dynamics and resistance evolution in the pathogenic bacterium Pseudomonas aeruginosa. We subjected two clones of bacterium to four doses of antibiotics and assessed growth and frequencies of public goods producing and non-producing genotypes. Our results show that abiotic stress selects against public goods production. Specifically, we found that non-producers of costly iron chelating molecules (siderophores) most rapidly increased in frequency under intermediate antibiotic pressure. Moreover, the dominance of non-producers in mixed cultures was associated with higher survival and resistance to antibiotics than in either producer or non-producer monocultures. Mathematical modelling explains this counterintuitive result, and shows how these qualitative patterns are predicted to generalise to many other systems. Our results shed light on the complex interactions between social traits and ecological antagonisms, and in particular the consequences for bacterial social evolution and antibiotic resistance.

Microbiology