Fiber photometry allows the activity of molecularly defined neuronal populations to be measured in freely behaving animals. The method is based on an implanted optical fiber through which fluorescent genetically encoded indicators of cellular activity, metabolites or signaling molecules can be monitored and is widely used in neuroscience research. However, conventional photometry systems are not flexible and typically limited to a fixed configuration of one or two readout channels. We will develop a new product based on a radically redesigned concept of fiber photometry called Fused Fiber Photometry (FFP). This new design is highly flexible and allows the fiber photometry setup to be easily reconfigured to a large number of spectral configurations at low cost. Furthermore, by combining spectral detection with spectral control of the fluorescence excitation signal, we will realize hyperspectral fiber photometry. Fused fiber photometry and hyperspectral photometry have the potential to gain large attraction in the academic research, industrial R&D and manufacturing processes, and in medical diagnosis. The technique has therefore high commercialization potential and a competitive advantage over existing commercial systems. It allows companies to offer a simple, out-of-the-box, turnkey system that can be easily modified and upgraded to meet user requirements. Our goal is to develop a commercializable hyperspectral fiber photometry system based on FFP. We will work hand in hand with established industrial partners to bring the system to market. By realizing HyFiPhotometry in this PoC project, want to exploit the full potential of hyperspectral photometry and demonstrate the feasibility of the basic idea. In the long term, we aim it to drive inventiveness in the fields of biomedical research, medicine and beyond. In this way, we expect to move our product from the niche of neuroscience to a wide range of applications that are highly relevant to society.

The behavior of many-body quantum systems is one of the most difficult problems in modern physics. An interesting and open question is how the properties of a complex many-body system depend on its constituents, and how collective behavior emerges from the underlying few-particle building blocks. Ultracold atoms offer the unique possibility to realize well-controlled quantum systems and study this question directly in the laboratory. We propose a highly adaptable approach to assembling systems of few ultracold fermions in optical micro traps. Using a spatial light modulator, we will implement arbitrary trapping potentials and small optical lattices with novel geometries. A near-deterministic loading scheme will initialize states with extremely low entropies and realize previously inaccessible quantum states. We will perform detailed measurements of static and dynamic spin orderings on small Mott insulating plaquettes and realize unusual cylindrical optical lattices with periodic boundary conditions. Our approach is complementary to many traditional optical lattice experiments and will generate wide interest in mesoscopic Fermi systems.

Biological activity of cells depends on timely production of natively folded proteins by powerful translation and folding machineries. At a critical regulatory intersection of translation and folding, ribosomes act as integration hubs coordinating chaperone, enzyme and membrane targeting factor activity, influencing folding. Final assembly of proteins into oligomeric complexes however, has long been considered post-translational and dependent on random collision of fully synthesized diffusing subunits. In a shift of paradigm, recent evidence from the Bukau laboratory now suggests that in bacteria, assembly initiates co-translationally assisted by chaperones, and gene organization into operons drives co-localized translation of complex subunits that impacts efficiency of assembly. Fundamental differences in eukaryotes such as rarity of operons and differing chaperone constellations imply a widely different folding and assembly biology, which remains largely unexplored. The selective ribosome profiling (SeRP) method, developed by the Bukau lab, now allows ground breaking identification and definition of dynamic interactions of nascent chains, at near-residue resolution. Using SeRP with supporting biochemistry, I will unravel the nascent chain molecular biology underpinning protein folding and assembly in yeast, Saccharomyces cerevisiae, a powerful model for studying the fundamental aspects of this biology. Specifically, I will establish (1) basic features and prevalence of co-translational protein assembly, (2) how chaperones guide co-translational protein folding to affect assembly. Subunit interaction profiles complemented by chaperone interaction profiles, will expose the timing and interplay of protein folding and assembly steps linked to protein synthesis, establishing a detailed conceptually new biology of complex assembly in eukaryotes.