Project: Molecular regulation of lactation: investigating DNA replication, transcription, and damage repair
Supervisor
Zuzana Sumbalová Koledová
Project description
Lactation is a critical physiological process requiring precise coordination of cellular functions, including DNA replication, transcription, and the DNA damage response, to support milk production. This PhD project aims to unravel the molecular mechanisms underlying these processes in lactating mammary epithelial cells. Using a cutting-edge lactation organoid model developed in our laboratory, combined with in vivo mouse models, the student will explore how DNA replication and transcription and DNA damage response regulate differentiation of luminal cells to milk-secreting alveolar cells. Advanced imaging techniques, transcriptomics, and molecular biology tools will be employed to investigate these pathways in detail. The findings will provide new insights into the fundamental biology of lactation and may identify novel targets for addressing lactation-related disorders, contributing to improved maternal and neonatal health.
Candidate profile
Strong interest in developmental, cell or cancer biology,
Master’s degree in biological sciences,
Highly motivated and independent with excellent communication skills,
Excellent organizational skills and the ability to maintain meticulous records, with ability to plan and prioritize own work in order to meet deadlines,
Ability to work collaboratively in a multidisciplinary research environment,
Strong written and verbal communication skills for data presentation and manuscript preparation,
Committed to personal development and updating of knowledge and skills,
Hands-on experience in work with genetic mouse models, organoids, live cell imaging, 3D immunofluorescence will be viewed positively.
Prior experience with DNA damage or mammary gland research will be considered an advantage.
Suggested reading
Sumbal J, Chiche A, Charifou E, Koledova Z, Li H: Primary mammary organoid model of lactation and involution. Front Cell Dev Biol.2020; 8: 68. [doi]
Molinuevo R, Menendez J, Cadle K et al. Physiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation. Nat Commun.2024; 15: 3288. [doi]
Rios A, Fu N, Jamieson P et al. Essential role for a novel population of binucleated mammary epithelial cells in lactation. Nat Commun. 2016; 7: 11400. [doi]
