Youths’ involvement in organized crime is worrisome, as it not only disrupts a healthy development, but also aggravates youths’ criminal behavior, and makes it harder to return to living a crime-free life. Social ties play an import role in the way youths get and stay involved in organized crime, that is why interventions are needed that target the youth, but also the youth’s social environment. We examine hotspots and mechanisms underlying organized crime involvement and use the knowledge gained to improve and implement intervention strategies. This way, the proposed project directly contributes to effectively decreasing youths’ involvement in organized crime.

The immune system is able to recognize and eliminate cancer cells when it is optimally activated. Cancer vaccines that can activate the immune system are expected to work synergistically with other treatments to improve the survival of cancer patients. Previously, we have demonstrated that Siglec-1/CD169-expressing macrophages can stimulate very strong immune responses. Our aim is to develop a new type of cancer nanovaccine that specifically targets cancer antigens to Siglec-1/CD169-expressing macrophages. In this project we will generate nanobodies that specifically can bind human Siglec-1/CD169 and incorporate these in cancer vaccines to enable efficient uptake by Siglec-1/CD169-expressing macrophages and the activation of immune responses that can eliminate cancer.

Regenerative medicine has made progress over the last years, but in the Netherlands, the field is still not well-connected. The field depends on research that combines different areas like stem cell technology, physics, bioelectronics, AI, medicine, and more. To create a clear national plan, experts from the NWA-route regenerative medicine and Stichting Toekomstbeeld der Techniek will work together. They will hold workshops and do research to understand important developments in technology, science, and society. The results will help create a strategy for the future of regenerative medicine and guide funding and policy decisions.

It can be very effortful to follow a conversation at a noisy party. By concentrating, you try to fill in the words that got lost in the noise. Focusing on the speech will help you to comprehend the message. However, you will become tired of listening. The aim of my study is to strengthen the basis for a new application of pupillometry (i.e., the measurement of pupil dilation) within the field of Audiology. Audiology currently needs a tool to objectively quantify the listening effort required during speech perception. Pupillometry is a promising candidate for an objective listening load index; my study will validate a novel application of this well-established effort measure. I will present speech in noise stimuli at a range of Speech-to-Noise Ratios (SNRs) and will relate the SNR, speech comprehension, brain activation, and the performance on relevant cognitive tests to listening effort as assessed by pupillometry. I will use functional Magnetic Resonance Imaging to identify the brain areas associated with effortful listening as reflected by the pupil response. Knowledge of the neural network involved in effortful listening will reveal the nature of the compensatory mechanisms supporting comprehension in difficult conditions. The combined examination of the pupil response, brain activation, and individual auditory and cognitive abilities will provide valuable knowledge in the interdisciplinary area between psychology, cognitive hearing science, and clinical Audiology. This study will contribute to the further development and confirmation of models of speech comprehension. Furthermore, insight into the factors influencing the pupil response, and knowledge of the neural origin of pupil dilation will provide the basis for implementing and interpreting an objective measure of listening effort. Once effortful listening can be quantified, it becomes possible to develop and evaluate strategies aimed to reduce the stress and fatigue caused by hearing difficulties.

Small GTP-binding proteins of the Rho family (RhoGTPases) control cell adhesion and migration as well as cell division and apoptosis. Consequently, RhoGTPases regulate tissue morphogenesis, immune responses and aging. These GTPases act as molecular switches: they are activated by RhoGEFs, Exchange Factors which catalyse the exchange of bound GDP for GTP, inducing a conformational switch required to trigger downstream signalling. Subsequent inactivation is induced by GTP hydrolysis, an intrinsic activity which is accelerated by RhoGAPs, GTPase Activating Proteins. Detailed insight in these mechanisms and their relevance for cellular functions is important, since uncontrolled GTPase signalling can cause neurological disorders, chronic inflammation or cancer. Intriguingly, we and others recently showed that inactivation of RhoGTPases also occurs through site-specific ubiquitylation by specific ligases, followed by internalization and degradation. However, it is completely unclear how, when or where GAPs, driving GTP hydrolysis, and ubiquitin ligases act in concert to regulate GTPase output. This project will focus on Rac1, a prototypical RhoGTPase. Our lab has shown that, in primary human endothelial cells, which is a well-studied model, both GAP-mediated and ubiquitylation-induced Rac1 inactivation occurs. We will establish the differential role, relevance and subcellular localization of the two modes of inactivation in response to receptor agonists or mechanical force. We will combine cell biological and -biophysical approaches in vitro and in vivo and focus on the control of cell-cell contact, adhesion and migration. Based on these fundamental studies, the project will formulate new concepts on GTPase regulation and the consequent control of key cellular functions.