CAU

I will use my MSCA-IF in the Stukenbrock Lab to dissect the molecular interactions between the fungal pathogen, Zymoseptoria tritici, and its host plant, wheat. Despite being the most devastating fungal wheat disease in Europe, little is known about the molecular mechanisms used by Z. tritici to cause disease. I propose to undertake a project that will use my expertise in molecular biology, combined with the Stukenbrock Lab's expertise in fungal genomics and evolution, to build a better understanding of how Z. tritici is able to evade host immune defences in order to grow, develop and, ultimately, induce disease symptoms. Plant pathogens use secreted proteins, described as effectors, to suppress host defences and/or alter host metabolism. However, few effectors from Z. tritici have been characterised. I aim to identify effectors that are used by Z. tritici to suppress wheat immune systems. To select effector candidates, I will use the Stukenbrock Lab's Zymoseptoria genomic resources to compare the variation in effector complements among Z. tritici and its closely related sister species. Z. tritici can infect wheat and not wild grass species. Inversely, Z. tritici's sister species infect wild grasses, but cannot infect wheat. Therefore, I hypothesise that effectors shared among all of these species are candidates as suppressors of conserved plant immune systems, whereas, effectors unique to Z. tritici, and conserved among all isolates of this fungus, are likely involved in host specialisation. I will screen the former set of effector candidates for their ability to suppress BAK1-dependent immune responses (an immune pathway conserved among a divergent range of plant species). I will knock-out the genes encoding the latter set of effectors, and will screen whether the virulence of the resulting mutants is reduced. Combined, these two approaches will help assign functions to more Z. tritici effectors and, thereby, develop new insights into this devastating disease.

Cells respond to external mechanical stimuli through an activation of a cellular mechanism called mechanotransduction. The cellular responses in this mechanism are expressed by a modification in cellular proliferation, migration and differentiation, as well as in a strengthening of their adhesion. Likewise, diseases such as cancer and cardiac dysfunctions are also related to cellular mechanotransduction. Here we propose to take a novel 3D material porous material towards commercial applications. The material serves as a platform for controlling mechanotransduction (e.g. in implant materials) and enables a control of mechanotransduction by mimicking natural 3D cellular environments. Our material contains a novel form of microporous structures represented by micron-sized channels embedded in a polymer matrix of a well-defined stiffness that has been developed within the ERC project CELLINSPIRED. The material guarantees pore interconnectivity independently of pore density and size, a unique feature offered by our fabrication procedure, for which we have applied for a patent (EP 15166793.8, PCT/EP2016/060160). Furthermore, it also provides a large, three-dimensionally controlled cell-surface contact area, such that the mechanical properties of the environment will have large impact on the cells. Our goal in this project is to validate our novel material for cellular applications where mechanotransduction is targeted. The expected outcome of our project is to receive a demonstrator material that (1) has well-defined mechanical properties, porosities and pore dimensions, (2) is biocompatible and can be sterilized, (3) can be fabricated in different levels of complexity, (4) can activate mechanotransduction in cells, and (5) can be fabricated using high-throughput processes. As for commercialization, we aim to license the patent to biomaterials companies involved in applications that range from 3D cell cultures to implant materials.

The project ‘MinErVa: Mid-Pleistocene Environments of the lower Vaal River’ seeks a multidisciplinary perspective on the effects of environmental change on human evolution by examining the palaeoenvironmental context of the first anatomically modern humans in the arid interior of southern Africa (c. 300-100ka). The MinErVa project is focused around the archaeological site of Pniel, an Early Middle Stone Age open-air site on the Vaal River that I have been excavating for two seasons since 2017. The site is located in an area with fossil evidence for early human evolution, however, there is a lack of terrestrial proxy records to reconstruct climate and environment during this time period. Specifically, the project will test the hypothesis that the local environment included phases of persistent wetness and significant biome shifts, caused by increased winter rainfall, though carbon and oxygen stable isotope analysis on herbivore teeth. Furthermore, MinErVa will apply innovative carbon and hydrogen stable isotope analysis on leaf wax n-alkanes in sediment to reconstruct vegetation and palaeohydrology. In a synthesis with isotopic, zooarchaeological, geomorphological, phytolith and lithic data sets recovered from my ongoing excavations, this project will explore how the first Homo sapiens were adapting to their environment. The project offers scope for testing the application of stable isotope analysis of leaf wax isotopes in sediment for the first time in a terrestrial context of this antiquity on South Africa and will therefore offer unique training to the applicant in a novel method which can has the scope to establish new proxy records in a region where there is a distinct lack of them.

The soil of the earth is the basis of our life. Efficient use of soil is needed for feeding the growing population. Contaminated soil needs to be regenerated to protect the quality of drinking water and more generally the ecosystem. Here, we propose a highly miniaturized sensor system for monitoring nitrate, ammonium, and phosphate based on integration of a lab-on-a-chip microfluidic cartridge with an optoelectronic detection unit. The optoelectronic detection chip employs the directional organic light emitting diode (OLED) we developed within the ERC PoC project BEAMOLED. This kind of OLED allows for direct integration of the optoelectronic chip with the microfluidic cartridge providing a new level of miniaturization of the optical readout measurement system. We propose the use of colorimetric assays based on starting with standard assays and improving performance using nanozyme catalysis. A hydrophilic ceramic as inlet to a microfluidic channel is proposed for intake of soil solution. Reagents as well as the waste are stored in the sensor system. We target a system size of 3 cm x 3 cm x 5 cm for maintenance-free operation in the soil for a duration of one year for in-situ monitoring of 100 data points per nutrient. In a soil-science study the soil-solution extraction into the microfluidic will be investigated for soils with a wide range of pore size distributions, bulk densities, pore-space connectivity, and soil water content to validate the extraction approach scientifically. Pot and field tests in agriculture and soil remediation are planned for validation in application-relevant environments of two potential markets and to develop market readiness. Our aim is to start a spin-off company after completion of this project. By the parallel development of the technology and business side with an interdisciplinary team from electrical engineering, chemical engineering, soil science, and economics/entrepreneurship an iterative adjustment process is achieved.