Dr Robert Mahen

Supervisor Details

Contact Details

Department of Molecular and Cell Biology, University of Leicester

Scientific Background

Research Interests

Life is sustained by the collective function of subcellular molecular machines termed organelles. Much is still to be understood about the assembly and function of organelles – a question which is critical to human health and disease.

We seek to understand the fundamental functions of centrosomes – microtubule-based organelles that allow cells to divide, move and sense their environment. Defects in centrosomes cause many poorly understood developmental diseases and are also implicated in carcinogenesis. Our work uses combined tools from fluorescence microscopy, genome editing and biochemistry, to understand the function of centrosomes across scales, with a long-term goal to treat human disease.

During cell division centrosomes form spindle poles, and thus are important for accurate chromosome segregation. My work has developed technologies to study centrosomes directly inside living cells, and proposed new models for how centrosomes are constructed from component parts during mitosis. Centrosomes also form cilia: hair-like appendages used for cell sensing and motion in a range of different human tissues. My recent work has pioneered imaging of cytoskeletal fibres nucleated by centrosomes termed rootlets, with a view to understanding human ciliary structure and function. We are collaborating with groups from across the University of Leicester to understand centrosome functions in human tissues from a multidisciplinary perspective.

Scientific Inspiration

Alan Turing, Marie Curie, Robert Oppenheimer. Giants who saw things differently and were aware of the wider context of their research.

Supervision Style

In three words or phrases: Supportive, inclusive, adaptive.

Provision of Training

I take responsibility for your initial training, providing a good foundation for independence later.

Progression Monitoring and Management

I will expect you to take full ownership of your progression but I am here for advice and guidance to help you reach the goals you set for yourself. I have an open-door policy for troubleshooting.

Communication

I am known to email my team/PhD students at all hours of the day and night, however I will not expect you to do the same. I am happy to discuss any issues that are impacting your ability to fulfil your potential or my/our expectations.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD Study

At least once per week

In year 2 of PhD Study

At least once per fortnight

In year 3 of PhD Study

At least once per fortnight

These one on one meetings will be a mixture of face to face and via video call or telephone, and I am usually contactable for an instant response on every working day.

Working Pattern

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Understanding centriole assembly in diverse human cells using advanced imaging and genomics

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Understanding centriole assembly in diverse human cells using advanced imaging and genomics

Secondary Supervisor(s): Dr Robert Hirst, Professor Edward Hollox

University of Registration: University of Leicester

BBSRC Research Themes:

Understanding the Rules of Life (Structural Biology, Systems Biology)
Integrated Understanding of Health (Regenerative Biology)

Project Outline

Centrioles are microtubule-based structures that form two different important cellular organelles: centrosomes and cilia. Centrosomes organise the microtubule cytoskeleton, and consequently have critical roles in cell division and cell polarity. Non-motile cilia are hair-like appendages present on most human cells that act as sensory antennae. Motile cilia function as extracellular propellers to move fluid – a function which is important in human tissues including the airway. Dysfunction of centrioles is linked to human pathologies including ciliopathies and cancer, and so understanding centriole function is both a fascinating fundamental question and a pressing concern for disease diagnosis and therapy. The Mahen lab is focused on understanding the mechanisms underpinning healthy and unhealthy centriole function, using tools including advanced light microscopy, genetics and organotypic culture (e.g. Mahen et al., 2012, PNAS; Mahen PLOS Biol., 2018).

Inside the lung, billions of motile cilia beat a million times a day to protect the airway from pollution and infectious agents. This mucociliary clearance is critical for respiratory epithelium health, and its dysfunction contributes to progression of diseases including primary ciliary dyskinesia and asthma. Whereas most cells contain just two centrioles, airway cells in contrast contain hundreds of centrioles per cell, each at the base of a cilium. How the activity, position and number of these centrioles is regulated to allow ciliary beating is still poorly understood. Remarkably, recent work in our lab has shown that airway centrioles are connected by a cytoskeletal meshwork of centriolar rootlets. Rootlets are fibres that have long been known from electron microscopy images, yet their functions are largely mysterious. Using expansion microscopy in organotypic cultures from human nasal brush biopsies, we have discovered that rootlets form branching networks, characterised by different types of morphological motifs. Many exciting questions have now arisen about this newly discovered structure (Fig. 1).

Fig.1: Rootlets form branching networks in human airway cells (Mahen, unpublished). (A-C) Rootlets (blue) and centrioles (red) visualised in human multiciliated cells with expansion microscopy and immunolabelling.

In this multidisciplinary project you will use combined advanced imaging technologies including expansion microscopy, super resolution live-cell imaging and electron microscopy to understand centrosomes at unprecedented resolution in human airway cell types. In parallel, we will use in silico analysis to discover how individuals in human populations have differing genetic variation that influences centriole structure in human tissues. This will allow us to create mutant in vitro lung models to understand the effects of this genetic variation.

The project will provide training in specialised skills from our expert team, as you learn state-of-the-art fluorescence imaging, organoid and air-liquid interface culture, and analysis of genomic structural variation. It is an exciting opportunity to discover fundamental mechanisms of organelle function that are important for human health.

Techniques

Techniques that will be undertaken during the project:

Live-cell time-lapse imaging.

Expansion microscopy.

Super-resolution microscopy (SIM, STORM).

Air-liquid interface and organoid culture.

In silico analysis of genomic structural variation.

Molecular cloning and genome editing (CRISPR Cas9, prime editing).

Electron microscopy.

Specialist techniques for cilia analysis, including high speed video microscopy.

References

Mahen, R. cNap1 bridges centriole contact sites to maintain centrosome cohesion. PLOS Biology. 2022. 20(10).

Mahen, R. The structure and function of centriolar rootlets. Journal of Cell Science. 2021. 134(16).

Co-supervisor on a project with Dr Kayoko Tanaka.

Previous Projects (2024-25)

Primary supervisor for:

Understanding centrosome function in the human airway

Co-supervisor on a project with Dr Kayoko Tanaka.