Integrated Calendar

Plants and apicomplexan parasites are more closely related than many might expect. Both evolved from a red algal ancestor and both still possess plastids. Plants have chloroplasts whereas apicomplexans like the malarial parasite Plasmodium falciparum have an apicoplast. This diminished ‘relic’ plastid is no longer photosynthetic, but remains essential for its production of isoprenoid precursors. Proof the apicoplast was of plant origin was provided, in part, by killing P. falciparum with herbicides. We recently turned this idea on its head asking whether drugs designed to treat malaria might be herbicidal and found many indeed were [1]. This has led us to apply the rapid advances in malaria research over the last decade to the stagnant field of herbicide discovery [2-3]. The success of glyphosate and spiralling cost of bringing new compounds to market stopped discovery programs by agrochemical companies and consequently, no new herbicide mode of action has reach the market in 20 years. Herbicide resistance has the world in a panic. Using antimalarial drug libraries and knowledge of malarial drug action we are attempting to put as many new modes of action ‘on the table’ as we can, each accompanied by an herbicidal molecule to probe each target [4]. A by-product of this applied work has already been knowledge about what, in many cases, are under-studied plant proteins [4].

[1] Corral, Leroux, Stubbs, Mylne (2017) Herbicidal properties of antimalarial drugs. Scientific Reports (PMID 28361906).
[2] Gandy, Corral, Mylne*, Stubbs* (2015) An interactive database to explore herbicide physicochemical properties. Org. Biomol. Chem. (PMID 25895669)
[3] Corral, Leroux, Tresch, Newton, Stubbs*, Mylne* (2017) Exploiting the evolutionary relationship between malarial parasites and plants to develop new herbicides. Angew. Chem. Int. Ed. Engl. (PMID 28654179)
[4] Various et al. (under review or in prep.) ... you have to come to find out more!

The replacement of fossil fuels by a clean and renewable energy source is one of the most urgent and challenging issues our society is facing today, which is why intense research is devoted to this topic recently. Nature has been using sunlight as the primary energy input to oxidize water and generate carbohydrates (a solar fuel) for over a billion years. Inspired, but not constrained, by nature, artificial systems [1] can be designed to capture light and oxidize water and reduce protons or other organic compounds to generate useful chemical fuels. In this context this contribution will present a variety of molecular water oxidation catalysts based on transition metal complexes, together with their activity in homogeneous phase and anchored on solid surfaces to generate electro- and photo-anodes. A detailed analysis of their performance will be discussed.

Textbooks of quantum mechanics lack the concept of the past of quantum systems. Few years ago I proposed to define the past of a quantum particle according the trace it leaves. While in many cases this definition provides a reasonable description, for a nested Mach-Zehnder interferometer it leads to a picture seemingly contradicting common sense: the particle leaves a trace in a place through which it could not pass. I will discuss recent theoretical and experimental studies of this controversial issue.

The deep space climate observatory (DSCOVR) spacecraft resides at the 1st Lagrangian point about one million miles from Earth, where roughly the solar pull balances the terrestrial one. A polychromatic imaging camera onboard delivers nearly hourly observations of the entire sun-lit face of the Earth. Many images contain surprisingly bright flashes of light over both ocean and land. We construct a yearlong time series of flash latitudes, scattering angles and oxygen absorption to demonstrate that the flashes over land are specular reflections off tiny cloud ice platelets. Such deep space detection of tropospheric ice can be used to constrain the likelihood of oriented crystals and their contribution to Earth albedo. These glints may help detecting starlight glints off faint companions in our search for habitable exoplanets.

Improving the binding affinity of protein-protein interaction is a major challenge in research, therapeutics and drug development. In antibodies, the process of somatic hypermutation and clonal selection leads the B cells to express high affinity binders. However, an undesirable side-effect is that affinity-enhancing mutations may reduce stability. We used deep mutational scanning to systematically map the mutational tolerance of an antibody variable fragment (Fv), finding that 20% of affinity-enhancing mutations occur at the interface between the light and heavy chains, away from the antigen binding site.
This interface mediates the interaction between the two chains that form the core of the antibody, and may therefore be responsible for both antibody stability and affinity. From the deep mutational scanning data, we learned general rules for stabilizing and improving the affinity of antibodies. Computational designed variants comprising 5-10 mutations in the light-heavy chain interface improve affinity by as much as an order of magnitude, and also improve thermal stability and aggregation resistance. Laborious cloning, selection, and sequence analysis can thus be averted through fully automated computational affinity and stability design.