The invention relates to muteins of the pyrroline-5-carboxylate reductase 1 (PYCR1), to nucleic acid molecules comprising a nucleotide sequence encoding such muteins, to methods of determining in a subject a predisposition of having an age related disorder associated with PYCR1, to methods of identifying a compound capable of modifying the expression of PYCR1, and methods of treating a subject having an age-related disorder associated with PYCR1. The invention further relates to a genetically modified animal and a method of modifying the expression of the PYCR1 gene in an animal.

The invention relates to muteins of the pyrroline-5-carboxylate reductase 1 (PYCR1), to nucleic acid molecules comprising a nucleotide sequence encoding such muteins, to methods of determining in a subject a predisposition of having an age related disorder associated with PYCR1, to methods of identifying a compound capable of modifying the expression of PYCR1, and methods of treating a subject having an age-related disorder associated with PYCR1. The invention further relates to a genetically modified animal and a method of modifying the expression of the PYCR1 gene in an animal.

A novel combinatorial and high-throughput platform that enables rapid screening of complex and heterogeneous copolymer brushes as enzyme immobilization supports named Combinatorial High-throughput Enzyme Support Screening (CHESS). Using a 384 well-plate format, we synthesized arrays of three-component polymer brushes in the microwells using photo-activated surface-initiated polymerization, and immobilized enzymes in situ. The utility of CHESS to identify optimal immobilization supports under thermally and chemically denaturing conditions was demonstrated using Bacillus subtilis Lipase A (LipA). The identification of supports with optimal compositions was validated by immobilizing LipA on polymer-brush modified biocatalyst particles. We further demonstrated that CHESS could be used to predict the optimal composition of polymer brushes a priori for the previously unexplored enzyme, alkaline phosphatase (AlkP). Our findings demonstrate that CHESS represents a predictable and reliable platform for dramatically accelerating the search of chemical compositions for immobilization supports and further facilitate the discovery of biocompatible and stabilizing materials.

The present disclosure relates to methods of identifying a subject as a candidate for cancer treatment and methods of treating cancer in a subject in need thereof according to the detection of plasma extracellular vesicles and/or plasma extracellular vesicle proteins. In addition, the present disclosure relates to kits comprising reagents and substrates for identifying a subject as a candidate for cancer treatment.