Understanding the mechanisms for consciousness is arguably one of the most intriguing questions of modern neuroscience. Why are some visual stimuli consciously perceived, whereas others remain subliminal? What is the relation between conscious perception, attention and working memory? Recent work of my lab demonstrated that weak but simple stimuli can be reported once they elicit a minimal level of activity in the frontal cortex, which is related to the storage of the stimulus in working memory. For these simple stimuli, the visual cortex acts as a relay station that needs to pass the information to higher cortical areas. However, we found that the perception of more complex visual stimuli relies on a more sustained interaction between visual cortex and associative brain regions, related to scene segmentation and visual attention. These recent results pave the way for a genuine understanding of mechanisms for consciousness, inspiring new paradigms that assess the awareness of stimuli while varying the demands on attention and working memory. The present proposal will be the first to compare the neuronal fate of simple and complex stimuli that do and do not enter consciousness across most brain regions. We will measure the activity of single neurons in human patients who are implanted with electrodes as part of their treatment of drug-resistant epilepsy. We will also use a new method that permits the recording from numerous single neurons within an entire hemisphere of a monkey and characterize neuronal activity in most regions of the cortex and subcortex. We will use perturbation methods at numerous locations throughout the brain in combination with functional imaging in monkeys to measure a “functional connectome” and to investigate the brain regions in which activity does (or does not) readily lead to a reportable experience. The proposed combination of experiments will provide unprecedented insight into how sensory stimuli give rise to conscious perception.

Over two million foreigners served in the ranks of the Wehrmacht and Waffen-SS. They came from different occupied territories and war zones, or even from uninvolved and neutral countries. These men had a significant impact on the war itself and how it was experienced and conducted. How these men from more than 40 countries experienced the war in German uniform as transnational soldiers remains a black box. TransWarSoldierWWII will trace the experiences of these soldiers by focusing on those who originated from the Benelux to determine the framework of the European war experience from a new angle. This research will deepen understandings of individual biographies of foreign soldiers in WWII from a transnational perspective. This new angle will open up the academic and public discussion on the involvement of non-German soldiers and their entanglement in the war and aims at a profound and critical analysis beyond nation-state narratives. I will be hosted at the Netherlands Institute for War, Holocaust and Genocide Studies (NIOD) in Amsterdam, where Professor Ismee Tames will supervise and mentor me. The research is premised on Responsible Research and Innovation. It will result in a symposium on transnational war experiences, two scientific articles in peer-reviewed journals and dissemination activities in public lectures and a podcast. The project's overall aim is to strengthen my research capacity and skills to assist in securing a leading research position that will enable me to contribute my knowledge and make a crucial impact on this field in military and social history.

The perception of complex visual scenes requires active processing by the brain. The visual cortex is hierarchically organized in several areas which are linked by connections projecting from lower to higher areas (feedforward) and connections projecting from higher to lower areas (feedback). More complicated processing occurs in higher areas such as V4, where neurons encode which side of a border belongs to a figure. Feedback connections are large in number but their function is poorly understood. An important role for feedback has been proposed in probabilistic inference, whereby cortical areas “infer” the reality in the external world based on the sensory information they receive from lower areas, combined with prior hypotheses projected down from higher areas. In this project we propose a causal study of the role of feedback connections from area V4 to lower areas in the inference of figure location. We will record neural activity simultaneously in V4 and V1, and V4 and V2, using microelectrodes in the awake rhesus macaque, during the presentation of figures on a background, while we reversible activate or suppress a well-defined patch in V4 using an opsin. By training the animal to perform a figure detection task we can link the perturbation of neural activity to perception. The beneficiary is the Netherlands Institute for Neuroscience, where the researcher will be advised by Prof. Pieter Roelfsema, an internationally recognized expert in visual neuroscience with experience with neurophysiology, behavioral studies and computational neuroscience. There will be an outgoing phase of two years, during which the researcher will perform animal experiments in the laboratory of Prof. John Reynolds in the Salk Institute for Biological Studies, who has extensive experience with optogenetics and viral targeting.

Self-organisation is a defining feature of living systems and entails complex interplay between multiple parameters across various spatio-temporal scales. Using pre-implantation mouse embryos as a model system, our studies revealed a principle of regulative development, in which feedback between cell fate, polarity and mechanics ensures robust control of embryo size, shape and pattern. However, as embryos undergo implantation, this self-organisation mechanism has to be integrated in its spatio-temporal context. In this project, we aim to understand how developmental mechanisms are coordinated in space and time. The peri-implantation mouse embryo is an attractive system in which to study this coordination, as it begins to interact with uterine tissues, marks a key transition in morphogenesis, cell cycle and growth, and exhibits a remarkable capacity for size regulation. We recently developed an ex vivo 3D culture, engineered uterus and light-sheet microscopy to recapitulate morphogenesis and embryo-uterus interactions, and analyse changes in cell shape, fate, polarity and mechanics. Using these new methods, we aim to mechanistically understand the transformation from blastocyst to egg cylinder as embryonic-extraembryonic tissues interact. We will use embryo size control as a paradigm to study the coordination of developmental programmes in space and time. At the cellular level, we will identify what triggers the transition from cleavage to proliferative cell cycle – mammalian mid-blastula transition. At the embryonic level, we aim to understand how animal size is sensed and changes the temporal progression of development. Finally, we will investigate the role of embryo-uterus interactions in embryo morphogenesis and positioning within the uterus. The bottom-up engineering approaches will be complemented by top-down intravital microscopy to monitor embryogenesis in utero. Together, this project will bring mammalian developmental biology into a new stage.

Inheriting one mutant copy of the BRCA1 or BRCA2 gene is associated with a significant increased risk for developing aggressive and difficult to treat breast cancer, the most common cancer type in women worldwide. Despite previous efforts to recapitulate tumorigenesis with the use of mouse models and cancer cell lines, the exact mechanisms that underlie BRCA1 or BRCA2-dependent tumor development remain unclear. Recent advances in stem cell culturing have enabled long-term expansion of in vitro human breast organoids or ‘mini-breasts’. In a novel approach, this state-of-the-art culture technology will be used together with CRISPR/Cas9-mediated gene-editing and human-in-mouse xenografts to prospectively recapitulate early breast cancer development. Results of the study will generate novel fundamental insight into the development of breast cancer, support the development of personalized medicine using laboratory models, and aspires to identify novel breast cancer biomarkers and treatment strategies. The expertise of the laboratory of H. Clevers, who pioneered the organoid methodology and works at the top of the field of stem cell biology, will be combined with the expertise of the research group of J. Visvader and G. Lindeman, world leaders in the field of breast cancer research and experts in the methodology of mammary xenotransplantation. This unique setting forms an excellent envorinment for my postdoctoral research training, allows extensive knowledge exchange and provides opportunities for novel research lines and collaborations.