In Nederland alleen al, worden er 5.500 nierpatiënten drie maal per week gedialyseerd, waarbij er een verbinding wordt gemaakt tussen het bloedvat en de dialysemachine en (hemodialyse). Om te kunnen dialyseren is er een goede toegang en efficiënt aanprikken van de bloedvaten nodig. Helaas wordt er in ongeveer 20-40% van de gevallen misgeprikt, met pijn, bloedingen, infecties, littekenvorming, vernauwing en uiteindelijk verstopping van de shunt tot gevolg. Het is lang bekend dat met behulp van echografie, bekend van o.a. zwangerschaps-echo’s, misprikken sterk kan worden verminderd. Bestaande echo-apparatuur is hier echter niet voor gemaakt, met als gevolg dat in de praktijk er nauwelijks met echo wordt gewerkt. De Vascoscope is een klein echo-apparaatje speciaal om het bloedvat goed aan te prikken. Zo wordt echo-geleid prikken toegankelijk en haalbaar voor elke dialyseverpleegkundige en dus voor iedere dialyserende nierpatiënt.

While all cells in the body contain the same DNA with the same genes, only a subset is activated in individual cells. This set determines the cellular identity and faulty selection often drives disease. Recently we learned that droplet formation by key proteins is crucial for gene activation. Using an “optical-tweezer” that can manipulate single molecules using infrared light to study these protein droplets we can finally obtain the level of detail needed to understand them. Insights enabled by this new technology will greatly improve understanding of gene control and may lead to new methods to inhibit faulty gene activation.

The decision to eat does not solely depend on our current metabolic state, but also on the value of the available food. This value is determined by both the rewards caloric-content and hedonic value, the degree to which food is experienced as pleasurable. As such, hungry animals will work harder for calorie-dense foods than rewards that has little- or no nutritional value. Likewise, rewards that are considered "pleasurable" will increase the motivational drive more than neutral or aversive rewards. Although this behavior is well described and of great importance to our understanding of reward-seeking behavior and eating disorders, the neurobiological mechanisms that mediate these choices are poorly understood. The aim of the experiments described in this proposal is two-fold; First, I will elucidate how reward value affects neuronal activity and behavior, and second, I will identify specific brain areas that mediate the metabolic and hedonic properties of reward. Therefore, I will measure neuronal activity of individual neurons in the rat brain while the animal is performing a decision-making task to obtain food rewards. In this task, the caloric-, and hedonic value of the rewards and the metabolic state of the animal (food-deprived or satiated) will be varied and I will assess how energy balance affects both reward-signaling as well as behavioral performance during task-execution. Secondly, I will inhibit the activity of specific neurons in rats that work to obtain food in the decision-making task. This approach will allow me to assess the role of very specific brain areas in the signaling of reward-information and ultimately decision-making. These experiments bring together the unique combination of two state-of-the art technologies "optogentics and in vivo electrophysiology" to elucidate the neurobiological substrate with which our brain processes cognitive- and metabolic information about reward and the manner in which the decision to eat is made.

In the last decade, biological medicine have become a more important therapeutic strategy with many new therapeutic possibilities, but the delivery of these medication on the right spot is still a challenge. In VINCI, we developed a nanosized drug-vehicle to increase circulating-time, reduced off-target effects and create a more effective therapy.

In this thesis, we describe the development, identification and characterization of four novel anti-complement nanobodies. This shows that the development of nanobodies against complement proteins is a good approach to develop these kinds of new molecules and tools. The nanobodies described in this thesis can be used now and in the future to further unravel important fundamental and clinical issues related to the complement system. In addition, some of these nanobodies could be used to develop new drugs that can inhibit overactivity of the complement system.