Background

I am a Sir Henry Dale Fellow (Group leader) at the Centre for Bacterial Cell Biology in the University of Newcastle, UK.

In my lab, we use advanced microscopy to figure out fundamental principles of bacterial spatial organization, focussing particularly on how bacteria divide and grow. We work at the interface between microbiology, biophysics and advanced microscopy.

Group website: Holden Lab website

VACANCIES We are always open to informal enquiries for PhD or Post-doctoral positions in this lab, and often find a way to fund good candidates. Please feel free to email me if you are interested (seamus.holden@ncl.ac.uk).

Research

- Bacterial cell division

- Physical principles of bacterial spatial organization

- Super-resolution microscopy

My research centres on studying the quantitative biology/ biophysics of bacteria, especially bacterial cell division, using single molecule fluorescence imaging and spectroscopy. I see bacteria as the perfect model system for the biophysicist. Their small size makes it possible to image the whole organism simultaneously, and utilising localization microscopy it is possible to localize nearly every molecule of a labelled protein with nanoscale resolution, within the living organism.

Teaching

Current teaching at undergraduate and masters level:
Lectures:

MMB8016    Molecular Microbiology    Lecturer

Research project supervision:

MRes project supervisor

Publications

• Perez AJ, Cesbron Y, Shaw SL, Villicana JB, Tsui HT, Boersma MJ, Ye ZA, Tovpeko Y, Dekker C, Holden S, Winkler ME. Movement Dynamics of Divisome Proteins and PBP2x: FtsW in Cells of Streptococcus pneumoniae . Proceedings of the National Academy of Sciences of the United States of America 2019, 116(8), 3211-3220.
• Sage D, Pham TA, Babcock H, Lukes T, Pengo T, Chao J, Velmuruga R, Herbert A, Agrawal A, Colabrese S, Wheeler A, Archetti A, Rieger B, Ober R, Hagen GM, Sibarita JB, Ries J, Henriques R, Unser M, Holden S. Super-resolution fight club: assessment of 2D and 3D single-molecule localization microscopy software. Nature Methods 2019, 16, 387-395.
• Lambert A, Vanhecke A, Archetti A, Holden S, Schaber F, Pincus Z, Laub MT, Goley E, Manley S. Constriction Rate Modulation Can Drive Cell Size Control and Homeostasis in C. crescentus. iScience 2018, 4, 180-189.
• Bisson-Filho AW, Hsu Y, Squyres G, Kuru E, Wu F, Jukes C, Dekker C, Holden S, VanNieuwenhze M, Brun Y, Garner E. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science 2017, 355(6326), 739-743.
• Mignolet J, Holden S, Bergé M, Panis G, Eroglu E, Théraulaz L, Manley S, Viollier PH. Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator. eLife 2016, 5, e18647.
• Holden S, Sage D. Imaging: Super-resolution fight club. Nature Photonics 2016, 10(3), 152-153.
• Bergé M, Campagne S, Mignolet J, Holden S, Théraulaz L, Manley S, Allain FHT, Viollier PH. Modularity and determinants of a (bi-)polarization control system from free-living and obligate intracellular bacteria. eLife 2016, 5, e20640.
• Carlini L, Holden S, Douglass K, Manley S. Correction of a Depth-Dependent Lateral Distortion in 3D Super-Resolution Imaging. PLoS One 2015, 10(11), e0142949.
• Min J, Holden S, Carlini L, Manley S, Ye JC, Unser M. 3D-FALCON: high-density 3D super-resolution microscopy via compressed sensing and astigmatic biplane imaging. Biomedical Optics Express 2014, 5(11), 3935-3948.
• Min J, Vonesch C, Kirshner H, Carlini L, Olivier N, Holden S, Manley S, Ye JC, Unser M. FALCON: fast and unbiased reconstruction of high-density super-resolution microscopy data. Scientific Reports 2014, 4, 4577.
• Holden S, Pengo T, Meibom K, Fernandez-Fernandez C, Collier J, Manley S. High throughput 3D super-resolution microscopy reveals Caulobacter crescentus in vivo Z-ring organization. Proceedings of the National Academy of Sciences of the United States of America 2014, 111(12), 4566-4571.
• Pengo T, Holden S, Manley S. PALMsiever: a tool to turn raw data into results for single-molecule localization microscopy. Bioinformatics 2014, 31(5), 797-798.
• Endesfelder U, Finan K, Holden S, Cook P, Kapanidis AN, Heilemann M. Multi-scale spatial organization of RNA polymerase in Escherichia coli. Biophysical Journal 2013, 105(1), 172-181.
• Holden S, Pengo T, Manley S. Optimisation and control of sampling rate in localisation microscopy. In: 10th International Conference on Sampling Theory and Applications. 2013, Bremen, Germany.
• Holden S, Uphoff S, Kapanidis AN. DAOSTORM: an algorithm for high density super-resolution microscopy. Nature Methods 2011, 8, 279–280.
• Torella JP, Holden SJ, Santoso Y, Hohlbein J, Kapanidis AN. Identifying Molecular Dynamics in Single-Molecule FRET Experiments with Burst Variance Analysis. Biophysical Journal 2011, 100, 1568-1577.
• Holden S, Uphoff S, Hohlbein J, Yadin D, Le-Reste L, Britton OJ, Kapanidis AN. Defining the Limits of Single-Molecule FRET Resolution in TIRF Microscopy. Biophysical Journal 2010, 99, 3102-3111.
• Uphoff S, Holden S, Le-Reste L, Periz J, van-de-Linde S, Heilemann M, Kapanidis AN. Monitoring multiple distances within a single molecule using switchable FRET. Nature Methods 2010, 7, 831-836.
• Lymperopoulos K, Crawford R, Torella JP, Heilemann M, Hwang LC, Holden S, Kapanidis AN. Single-Molecule DNA Biosensors for Protein and Ligand Detection. Angewandte Chemie International Edition 2010, 49(7), 1316-1320.