Anjali Kumari Singh

Repetitive sequences in the genome serve as hotspots for genetic variation. Repeat expansions in the coding regions of the gene could result in single amino acid homorepeat (HR) expansions in the corresponding protein, which has been linked to several neurodegenerative and developmental disorders. Although these hypermutable elements are detrimental, about 15% of the eukaryotic proteins contain homorepeats, indicating that HRs could have physiological functions. Accumulating evidences from various research groups, including ours, suggest that HRs are functionally versatile and might be involved in diverse processes such as gene expression regulation, signalling and cell-cell communication. However, how HRs affect cellular functions in various biological contexts remains unknown. HRs contribute to rapid adaptability in two ways (i) genetically, by accelerating accumulation of standing genetic variation and (ii) biochemically, by facilitating molecular interactions across diverse pathways and rewiring molecular networks. While isolated studies link protein HRs with different biological roles, a comprehensive systems-wide understanding of the role of HRs is lacking.

During my Ph.D. research work, we have investigated (i) the role of human proteins with HRs (HRPs) in influencing organismal fitness, (ii) how repeat co-occurrences influence protein functionality in humans and (iii) how HRPs facilitate host-pathogen interactions and influence pathogenicity of human infectious agents. We have (i) shown that HRPs constitute a rapidly evolvable and human-specific essentialome with key roles in human brain development, with implications for studying how repeat length variation can affect brain development and its functions, (ii) mapped the functional landscape of the co-occurring amino acids in human proteins, with implications for engineering proteins to obtain desired functions and (iii) decoded the amino acid repeat signatures underlying the human-pathogen interactions, with implications for targeting HRs and HRPs for therapeutic intervention.

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My Ph.D. studies involve and integrate many aspects of biology to obtain a systems-level understanding of the context-dependent physiological roles of HRs in host and pathogen physiology. I have undertaken computational and/or experimental studies spanning Molecular and Evolutionary Systems Biology, Comparative Genomics and Molecular Biology.