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Disease Mechanisms
Program Leader Track

Pleasantine Mill

Contact Details

E-mail address:
Telephone: +44 (0)131 651 8541
Fax: +44 (0)131 651 8800
Address: MRC Human Genetics Unit MRC IGMM, University of Edinburgh Western General Hospital, Crewe Road, Edinburgh EH4 2XU
Research Programme:

Genetics of Cilia Biology




Dr Mill received her BSc degree from McGill University and then went on to do a PhD with Prof Chi-chung Hui at the University of Toronto. Her work focused on dissecting the roles of the Gli transcription factors in Hedgehog signaling in skin development and tumorigenesis using knock-out and transgenic mouse models. Upon completion of her PhD, Pleasantine received a Canadian NSERC Post-doctoral Fellowship to continue her work in Developmental Genetics with Prof Ian Jackson at the MRC Human Genetics Unit in Edinburgh driving a mouse mutagenesis project to identify genes controlling neural crest development. As a Caledonian Research Fellow, Pleasantine focused on characterizing several mutant mouse lines that exhibited hallmarks of deregulated signaling through defects in cilia structure and/or function. This work led her to develop a cilia-centric research programme using siRNA cell-based screens and targeted mouse mutants to discover and understand genes critical to ciliogenesis.


Academic Qualifications 

    • 2004, Doctor of Philosophy, Medical and Molecular Genetics, University of Toronto, Canada
    • 1999, Bachelor of Science, Microbiology and Immunology, McGill University, Canada


Research in a Nutshell

Cilia are specialized microtubule-based structures found on the surface of most mammalian cells. They play key sensory and sometime motile functions. When cilia go wrong, either through defects in their assembly or function, they can have devastating effects on human development (birth defects) or postnatal health, where cilia dysfunction underlies blindness, kidney failure and infertility. This broad group of genetic disorders is termed ciliopathies.  We know that hundreds, if not thousands of genes are involved in building and maintaining this highly conserved organelle. But for the most part, we know very little about which and how individual genes are required for specific ciliary functions.


My lab uses the power of genetics combined with the latest molecular and cellular biology tools to address the following questions: How do we build the basic blueprint required for core cilia function? How is this basic genetic program elaborated on for specific ciliary functions, like ciliary motility? What can we learn about cilia gene function from human disease alleles?


There are four areas of interest in our lab:


1. Evolutionary genetics

In collaboration with Prof. Andrew Jarman (Centre for Integrative Physiology, University of Edinburgh), we use the power of genetics to identify potential cilial disease candidates in the relatively simple fruit-fly model to guide our mammalian studies, done mostly in mice.


2. Genetic screens

We have carried out phenotype-driven forward genetics (ENU mutagenesis) screens and reverse genetics (candidate siRNA) high-content cell-based screens to dissect the functional complexity of cilia.


3. Human disease genetics

We work closely our clinical genetics collaborators to identify and characterize human ciliopathy alleles. We use the CRISPR/CAS9 system of gene editing to build better models of human disease candidates to correlate genotype with cellular phenotype and overall health. We examine the effects of these mutations integrating microscopy, transcriptomics and proteomics. Taken together, we hope to develop evidence-based strategies for clinical management of ciliopathies, and perhaps even a cure.


4. Super-resolution and live imaging

Primary cilia are small, dynamic structures whose imaging is very much limited by these characteristics in terms of time and resolution. We aim to build tools to better capture events on a finer-scale across time and space using confocal, super-resolution (SIM, SPIM, PALM) and electron microscopy.