The Open Competition Domain Science – XS grants of a maximum of € 50,000 are intended to support promising ideas and to facilitate innovative and more speculative initiatives within the seven Domain Science disciplines. The proposed research is ground-breaking and high-risk. What counts is that all results, be they positive or negative, must contribute to the advancement of science.
The assigned VU applications (in alphabetical order of the applicant):
Neuroscientist Sanne Beerens for her resarch The ying and yang of memory: dissecting the molecular signature of useful versus pathological aversive memories.
An aversive experience can result in a memory that is beneficial for steering future behavior, but can also generate a pathological memory, as in posttraumatic stress disorder (PTSD). Research in mice revealed that memory-encoding neurons in the prefrontal cortex (PFC) are involved in retrieval of a mild, but not strong, fear memory, similar to reduced function of the PFC in PTSD patients. Beerens will investigate molecular changes in the synaptic structures that are important for communication between memory-encoding PFC neurons after aversive experiences with different intensities. This has high potential to yield novel entry points for intervention for traumatic memories.
Judy van Beijnum (Amsterdam University Medical Center) for her resarch Energy Heist: How Cancer Steals CAR T Cell Power During Attack
CAR T-cell therapy is a form of cancer therapy, which uses genetically modified (immune) T cells to kill cancer cells. If successful, it is curative, unlike other therapies. Failure occurs, often due to T-cell exhaustion. This can be linked to mitochondria, the energy factories of a cell, that can be hijacked by cancer cells . This leads to energy depletion and impaired killing. This study aims to investigate whether mitochondrial transfer occurs when CAR T cells and cancer cells interact, and how this impacts CAR T cell function.
PhD candidate in fluorescence microscopy, cellular metabolism, and signaling Dennis Botman for his resarch Efficient screening of sugar transport inhibitors for the sleeping-sickness parasite Trypanosoma brucei
Trypanosoma brucei causes deadly African sleeping sickness. Inside humans, this parasite depends on sugar to grow which makes sugar transport a prominent drug target. Botman wants to develop an efficient screening platform for sugar transport inhibitors of T. brucei. He will express T. brucei sugar transporters in yeast lacking its own transporters, add inhibitors and monitor growth. Effective inhibitors can serve as lead compounds for drugs. This method can also be used for cancer as they often also rely heavily on sugar breakdown. Potential risks include improper transporter functioning in yeast or low final efficiency if T. brucei adapts.
Iddo Heller for his resarch You’re as cold as ice, but not willing to sacrifice your life?
What do space travelers, crop protection, organ- and food-preservation, and climate-change-related ice restructuring have in common? All involve solid-liquid mixtures in which thermodynamically driven (ice-)recrystallisation processes can cause harmful/fatal crystal growth. Nature has evolved ingenious ways to inhibit ice-recrystallisation, which allows insect survival even down to -70oC. We propose to use theory and single-molecule experiments to uncover how nature uses ice-binding proteins to control recrystallisation processes. Uncovering these fundamental principles for the first time implies a breakthrough with exciting potential applications in engineering (synthetic) protectants for use in cryopreservation, medical applications, and… perhaps even space travel.
Jianfeng Jin (Academic Centre for Dentistry Amsterdam) for his resarch In Vitro Diabetic Implant Model with Integrated Mechanical Loading
Dental implant failure rates in diabetic patients reach ~14%, far exceeding the 2-5% in non-diabetic individuals, causing implant loss. This grant aims to build an innovative cell culture model of dental implants in a diabetic environment. The model consists of a hydrogel, a mimicry of a dental implant, bone cells, and mechanical force simulating chewing, in a high-glucose environment replicating diabetic oral conditions. The hydrogel mimicking the extracellular environment supports the bone cells allowing cell-cell/cell-implant interactions in an environment mimicking diabetic challenges. This model might have great potential to improve the accuracy and efficiency of dental implantology in diabetic patients.
Amga Laheij (Academic Centre for Dentistry Amsterdam) for her resarch Harnessing Prebiotics to Modulate the Oral Microbiota: A Pathway to Enhanced Oral Health?
The incidence of cancer is increasing, which means that many people are dealing with (serious) side effects of cancer therapy, including oral mucositis (40-100%, depending on cancer therapy). It causes pain, oral infections and problems with eating and drinking, and leads to malnutrition and a lower quality of life. Currently no effective treatments are available. Because oral mucositis is related to bacterial changes in the mouth, making the microflora healthier could be an innovative way to treat oral mucositis. We aim to reduce oral mucositis in a rat model by applications of the bacterial species Streptococcus dentisani.