The loss of neuronal function in Alzheimer’s disease is caused by aggregates in the brain. A modification of a protein, called protein tau, induces aggregation. Therefore researchers need to undo this modification, thus preventing the formation of toxic aggregates. This can be done using a technology called PhosTAC that redirects proteins already present in the human brain to restore healthy tau.

The nuclear pore complex (NPC) is one of the largest complexes in our cells and is the gateway between the cytoplasm and the nucleus, where our genetic information is stored. The selectivity of the gateway ensures passage of designated cargo. NPC integrity is crucial for many cellular functions, and disfunction is implicated in ageing and disease. Recent studies provided detailed insights into the structure of the NPC, but its assembly, the quality control during assembly, and the rearrangements of the nuclear envelope that take place to accommodate new NPCs, are largely enigmatic. The goal of the proposed study is to understand the mechanisms that drive and control NPC biogenesis. I will conduct a genome-wide CRISPR screen to identify the fusogen responsible for nuclear envelope fusion during NPC assembly. Further, I will study how the components of the NPC that contain large glycine/phenylalanine-rich disordered regions that make up the transport barrier, the FG-Nups, are targeted to biogenesis sites without undergoing premature phase separation. Overall, I aim to uncover key mechanisms and checkpoints in NPC biogenesis to deepen our understanding of NPC assembly and to gain insight into why NPC deterioration is fundamental to pathological states.

The brain is key for proper blood sugar levels regulation. Unexpectedly, it has been found that the reward area in the brain important for motivational behavior can detect sugar and influence blood sugar levels. This project investigates how and when this brain region regulates this, and how knowledge can be used for better treatment of diabetes.

Biological engineers are developing increasingly sophisticated technical measures intended to mitigate environmental, safety and security effects of synthetic biology. Research on methods of intrinsic biocontainment have progressed from simple kill switches to multiple nutrient dependency strategies to reduce fitness and engineered genetic codes to limit horizontal gene transfer. Research to date has focused on lab strains of E.coli rather than commercial chassis as model organisms. Furthermore, containment methods have not been the objects of independent technical testing or of systematic multistakeholder informed risk assessments. The proposed research and utilization plan is designed to fill these gaps in existing work and will pave the way for a systematic risk assessment and, where applicable, risk management of microbes of industrial interest.