Molecular profiling of altered cell states in renal ciliopathies

Supervisor details: Prof Pleasantine Mill pleasantine.mill@ed.ac.uk

Application deadline: 16/03/2025

Anticipated start date: 08/09/2025

Funding information (students eligible to apply) - UK/International students

This project is part of Cilia-AI (European Training Programme for Deconvolution of Multi-scale Cilia Function in Health and Disease by Integrating Machine Learning-AI Approaches: https://www.cilia-ai.eu), a Marie Sklodowska-Curie Doctoral Network (2025-2028), offering a cohort of 14 PhD positions. The objective of Cilia-AI is to train the next generation of interdisciplinary biomedical researchers and entrepreneurs using an array of machine learning approaches to aid in closing the knowledge gaps in ciliary function at molecular, cellular, and organ development level. 

Based at the Institute for Genetics and Cancer at the University of Edinburgh, UK, this project Molecular profiling of altered cell states in renal ciliopathies (ADC) 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-derived cells. 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. During this project, there will involve secondments to the Imagine Institut, France and the University of Tübingen, Germany to upskill in additional techniques and emerging areas.  

Additional Information 

Benefits: Marie Sklodowska-Curie PhDs are paid a competitive gross Living Allowance of 3,400 €/month, adjusted for their host country, a Mobility Allowance of 600 €/month and, for researchers who have a family, a Family Allowance of 660 €/month. All amounts are subject to deductions and taxes. Family is defined as persons linked to the researcher by (i) marriage, or (ii) a relationship with equivalent status to a marriage recognised by the national legislation of the country of the beneficiary or of nationality of the researcher, or (iii) dependent children who are actually being maintained by the researcher. 

To apply for this PhD position, the applicant must fulfil the following conditions: 

Applicants should hold (or be about to obtain) a UK or international 1st class or 2.1 degree or a Masters in any relevant discipline in biological or biomedical sciences + interest in rare genetic disease, genomics, cell biology or imaging. 

Trans-national mobility: The applicant — at the date of recruitment — should not have resided in the country where the research training takes place for more than 12 months in the 3 years immediately prior to recruitment, and not have carried out their main activity (work, studies, etc.) in that country.  For refugees under the Geneva Convention (1951 Refugee Convention and the 1967 Protocol), the refugee procedure (i.e. before refugee status is conferred) will not be counted as ‘period of residence/activity in the country of the beneficiary’. 

For more information about the Mill lab, please visit www.cilialab.co.uk 

References:

Dodd DO, et al. Ciliopathy patient variants reveal organelle-specific functions for TUBB4B in axonemal microtubules. Science 384, eadf5489(2024). DOI:10.1126/science.adf5489

Mill P, Christensen ST, Pedersen LB. Primary cilia as dynamic and diverse signalling hubs in development and disease. Nat Rev Genet. 2023 Jul;24(7):421-441. doi: 10.1038/s41576-023-00587-9.

Waddell SH,  et al. A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease. Sci Transl Med. 2023 Sep 13;15(713):eabq5930. doi: 10.1126/scitranslmed.abq5930.

Subject areas:

• Categories
• Biological Sciences
• Bioinformatics; Cell Biology; Genetics; Genomics; Human Genetics; Molecular Biology; Molecular Genetics 
• Computer Science
• Artificial Intelligence; Machine Learning;