Research Projects

The ubiquitin-proteasome system (UPS) is crucial for maintaining cellular homeostasis in eukaryotic cells, and its imbalance can lead to various diseases, including neurological ones like Alzheimer's and Parkinson's. Aneuploidy, an unbalanced number of chromosomes, causes proteotoxic stress, which overburdens the UPS in cells. These conditions have a significant impact on human health, with 90% of tumors being aneuploid. Proteotoxic stress, caused by perturbed protein complexes, is a hallmark of cancer, with 90% of tumors being aneuploid. Proteotoxic stress has been found in hybrids of fungi, plants, and animals, suggesting it as a general speciation mechanism. To understand how haploid and diploid introgressed hybrids resolve proteotoxic stress, researchers experimentally evolved both haploid and diploid hybrids that were most affected by proteotoxic stress. Both haploid and diploid hybrids became significantly fitter than ancestors, but evolved diploids demonstrated multi-chromosomal aneuploidy, while evolved haploids were mainly uni-chromosomal aneuploid without aneuploid S. uvarum chromosome. Interestingly, both haploid and diploid evolved lines garnered very few unique SNPs and indels, suggesting aneuploidy as the driver for adaptation. The project aims to dissect the mechanisms underlying contrasting modes of adaptation of haploid and diploid hybrids towards proteotoxic stress by determining protein complex architecture, protein interactions, and the source of differences in their adaptive response towards proteotoxic stress.