ADC14

Molecular profiling of altered cell states in ciliopathies (WP3)

Supervisor: Prof Pleasantine Mill

Host institute: University of Edinburgh, United Kingdom

Secondments: Institut Imagine, France; University of Tübingen, Germany

Doctoral Program: University of Edinburgh

** Associated Doctoral Candidate - will be administered and funded by the UK Research and Innovation **

I’m Sreeja Mitra from India, where I did my BSc in microbiology at Ramnarain Ruia College. While working on a proteomics-based project in mitochondrial homeostasis at Advanced Centre of Treatment Research and Education in Cancer (ACTREC), Mumbai, I realized the importance of high-throughput technologies in enabling cell biology research. A year later I started my MSc in genomic data science at the University of Leeds and worked on benchmarking a novel algorithm developed by my supervisors and senior for gene regulatory network inference on single-cell transcriptomic data. I found the perfect opportunity to chase the integration of proteome and genome in Professor Mill’s lab, where I have been welcomed for the next three years to dissect ciliopathies.

On the weekends I can be found in museums, anime conventions, or more often cooking mangsho bhaat.

ADC14: Molecular profiling of altered cell states in renal ciliopathies

ADC14 aims to understand how gene variants disrupt function at an organelle, cellular and physiological level in syndromic ciliopathies, using a novel humanized mouse model and matched patient-derivedcells. Focussing on kidney, we will (1) assess altered ciliary content by proximity labelling quantitative mass spec; (2) map altered cell states with spatial transcriptomics and proteomics; and (3) monitor changes in tissue architecture using quantitative imaging from onset of cystic disease. We will utilize AI-driven and ML approaches to integrate how changes in cilia content are related to cellular and metabolic rewiring of the microenvironment during syndromic disease and identify possible biomarkers and targetable pathways that could be explored for future therapeutic strategies.

The UK participates as associated partner, therefore the Associated DC position will be administered and funded by the UK Research and Innovation (UKRI).

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DC13 Interpreting non-coding and structural genomic variation in renal ciliopathies