Project 8

Evolutionary significance of mixtures of defense chemicals in trophic interactions

Supervisors:
Prof. Dr. Stefan Schuster (main supervisor)
Dept. of Bioinformatics, Matthias Schleiden Institute, University of Jena
Prof. Dr. Jonathan Gershenzon (co supervisor)
Department of Biochemistry, Max Planck Institute for Chemical Ecology

Background:
In many trophic (and parasitic) interactions, the prey organisms defend themselves by toxic compounds (defense chemicals). Many of the attacking organisms (e.g. herbivores), in turn, produce enzymes degrading the toxins. This can be considered as a counter-defense [3]. Many defense chemicals occur as mixtures of several similar compounds. For example, glucosinolates in Brassicaceae plants occur in various versions and chain lengths [4] and the cocoa plant produces several methylxanthines such as theobromine, theophylline and caffeine.

Project description:
One might argue that mixtures of several similar defense chemicals increase the effect on the attacker. On the other hand, the attacking organism could respond by producing detoxification enzymes with broader substrate specificity. Rather, the advantage of mixtures may be that some chemicals may act as competitive inhibitors of those enzymes. This can then be viewed as a counter-counter defense in combination with direct defense. Defense compounds might then act both as substrates and inhibitors of the enzyme, but this possibility has not been tested theoretically or experimentally.
In this project, we will attempt to derive kinetic equations for detoxification enzymes to determine whether mixtures of defensive chemicals might have an evolutionary advantage. The approach will be based on earlier work in enzyme kinetics [2,5], and will involve methods of mathematical optimization. Previous research on fatty-acid oxidation [1,5] is also relevant, since the enzymes for chain shortening of a given fatty acid may be subject to competitive inhibition by fatty acids of other chain lengths. In particular, we seek to identify conditions in terms of Michaelis constants and inhibition constants under which adding a further defense chemical to the mixture is favorable in comparison to increasing the concentration of the existing toxins.
The results may have practical relevance for future applications in plant protection and pharmacology (e.g. overcoming drug-resistant pathogens with mixtures of antibiotics).
The candidate can work in a productive bioinformatics/mathematical biology environment at Jena University and can benefit from a close cooperation with an experimental group at the MPI-CE Jena. If desired by the candidate, s/he can perform experiments in addition to the theoretical work.

Candidate profile:
The ideal candidate should have a master degree, preferably in bioinformatics, biomathematics, biochemistry or similar disciplines. S/he should have a strong background in mathematical modelling, computer science and the biological aspects of this topic.

Reading:

Abegaz, F., Martines, A. M. F., Vieira-Lara, M. A., Rios-Morales, M., Reijngoud, D. J., Wit, E. C., Bakker, B. M. (2021) Bistability in fatty-acid oxidation resulting from substrate inhibition. PLoS Comput Biol. 17 e1009259. https://doi.org/10.1371/journal.pcbi.1009259
Schäuble, S., Stavrum, A. K., Puntervoll, P., Schuster, S., Heiland, I.(2013) Effect of substrate competition in kinetic models of metabolic networks. FEBS Lett. 587, 2818-2824. https://doi.org/10.1016/j.febslet.2013.06.025
Schuster, S., Ewald, J., Dandekar, T., Dühring, T. (2019) Optimizing defence, counter-defence and counter-counter defence in parasitic and trophic interactions - A modelling study. arXiv: 1907.04820. https://doi.org/10.48550/arXiv.1907.04820
Textor, S., de Kraker, J. W., Hause, B., Gershenzon, J., Tokuhisa, J. G. (2007) MAM3 catalyzes the formation of all aliphatic glucosinolate chain lengths in Arabidopsis. Plant Physiol. 144, 60-71. https://doi.org/10.1104/pp.106.091579
van Eunen, K., Simons, S. M. J., Gerding, A., Bleeker, A., den Besten, G., et al. (2013) Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload. PLOS Comp. Biol. 9: e1003186. https://doi.org/10.1371/journal.pcbi.1003186