Dr Seamus Holden

Associate Professor

Email: seamus.holden@warwick.ac.uk

Phone: 024 765 75794

Office: IBRB2.28

Twitter: @seamus_holden

Holden lab website

Research Clusters

Microbiology & Infectious disease

Quantitative, Systems & Engineering Biology

Vacancies and Opportunities

For PhD and postdoctoral opportunities, and interest in potential collaborations, please contact me at the above email address.

Research Interests

My lab uses advanced microscopy to figure out how bacteria grow and divide. We study how proteins act as tiny nanoscale machines to build complex biological structures, with a particular focus on how bacteria remodel their cell envelope, which is one of the most important targets for antibiotics. To achieve this we use single molecule microscopy to follow the activity of individual proteins at nanoscale resolution inside live bacteria

Research: Technical Summary

My lab studies biophysical principles of bacterial cell wall biosynthesis, with a particular focus on the mechanistic principles of bacterial cell division and elongation. We work primarily with the Gram-positive model organism Bacillus subtilis. To tackle these questions my lab develops novel experimental methods based on single molecule & super-resolution fluorescence microscopy, microfabrication and microfluidics. I am a strong supporter of open science, and work to ensure that all of the software, methods and resources that my lab develops are freely available and easy to use.

About the lab

We are a diverse interdisciplinary lab combining approaches from molecular microbiology, physics, microscopy and data science. We are funded by the Wellcome Trust and BBSRC, and work with multiple national and international collaborators, including David Roper (SLS), Phill Stansfeld (SLS) at Warwick, and colleagues in Belfast, Newcastle, Cambridge, Austria and Australia.

Job/ studentship opportunities

If you would like to discuss any of the opportunities below, please send an email to seamus.holden@warwick.ac.uk, with CV.

Staff

Post-doc position in in vitro single molecule biophysics and super-resolution microscopy. Application deadline: 21 Nov 2023.

Senior Research Technician in biochemistry and molecular biology - post is joint with David Roper lab. Application deadline: 21 Nov 2023.

PhD and MBio students

We are happy to recruit PhD students via either the BBSRC MIBTP programme or the Warwick MRC DTP programme. We can also host MBio projects from the School of Life Sciences undergraduate degree programmes

I am very happy to supervise interdisciplinary projects to students from a range of training backgrounds such as biology, biochemistry, physics.

Undergraduate research projects

See "Teaching/ Student supervision" tab below.

Biography

2022: Moved to University of Warwick as Associate Professor (Reader).
2020: Awarded British Biophysical Society Louise Johnson Early Career Award
2018: Promoted to Principal Research Associate, Newcastle University.
2017: Awarded Wellcome Trust & Royal Society Sir Henry Dale Fellowship.
2015: Moved to Newcastle University to start independent research career.
2012: Awarded Marie Curie Intra-European Fellowship
2011-2015: Post-doctoral Researcher in laboratory of Professor Suliana Manley, EPFL, Switzerland,
2007-2011: DPhil in Biological Physics in laboratory of Professor Achilles Kapanidis, University of Oxford
2003-2007: Studied Physics, University of Oxford

Publications

Tab content

Whitley, Kevin D., Grimshaw, James, Roberts, David M., Karinou, Eleni, Stansfeld, Phillip J., Holden, Séamus, 2024. A one-track model for spatiotemporal coordination of Bacillus subtilis septal 2 cell wall synthesis. Nature Microbiology
Whitley, Kevin D., Grimshaw, James, Roberts, David M., Karinou, Eleni, Stansfeld, Phillip J., Holden, Séamus, 2024. Peptidoglycan synthesis drives a single population of septal cell wall synthases during division in Bacillus subtilis. Nature Microbiology
Whitley, Kevin D., Middlemiss, Stuart, Jukes, Calum, Dekker, Cees, Holden, Séamus, 2022. High-resolution imaging of bacterial spatial organization with vertical cell imaging by nanostructured immobilization (VerCINI). Nature Protocols, 17 (3), pp. 847-869
Spahn, Christoph, Gómez-de-Mariscal, Estibaliz, Laine, Romain F., Pereira, Pedro M., von Chamier, Lucas, Conduit, Mia, Pinho, Mariana G., Jacquemet, Guillaume, Holden, Séamus, Heilemann, Mike, Henriques, Ricardo, 2022. DeepBacs for multi-task bacterial image analysis using open-source deep learning approaches. Communications Biology, 5
Whitley, Kevin D., Jukes, Calum, Tregidgo, Nicholas, Karinou, Eleni, Almada, Pedro, Cesbron, Yann, Henriques, Ricardo, Dekker, Cees, Holden, Séamus, 2021. FtsZ treadmilling is essential for Z-ring condensation and septal constriction initiation in Bacillus subtilis cell division. Nature Communications, 12 (1)
von Chamier, Lucas, Laine, Romain F., Jukkala, Johanna, Spahn, Christoph, Krentzel, Daniel, Nehme, Elias, Lerche, Martina, Hernández-Pérez, Sara, Mattila, Pieta K., Karinou, Eleni, Holden, Séamus, Solak, Ahmet Can, Krull, Alexander, Buchholz, Tim-Oliver, Jones, Martin L., Royer, Loïc A., Leterrier, Christophe, Shechtman, Yoav, Jug, Florian, Heilemann, Mike et al (Select to open full list), 2021.

All authors for Democratising deep learning for microscopy with ZeroCostDL4Mic

von Chamier, Lucas, Laine, Romain F., Jukkala, Johanna, Spahn, Christoph, Krentzel, Daniel, Nehme, Elias, Lerche, Martina, Hernández-Pérez, Sara, Mattila, Pieta K., Karinou, Eleni, Holden, Séamus, Solak, Ahmet Can, Krull, Alexander, Buchholz, Tim-Oliver, Jones, Martin L., Royer, Loïc A., Leterrier, Christophe, Shechtman, Yoav, Jug, Florian, Heilemann, Mike, Jacquemet, Guillaume, Henriques, Ricardo

Democratising deep learning for microscopy with ZeroCostDL4Mic. Nature Communications, 12 (1)
Wu, Ling Juan, Lee, Seoungjun, Park, Sungshic, Eland, Lucy E., Wipat, Anil, Holden, Séamus, Errington, Jeff, 2020. Geometric principles underlying the proliferation of a model cell system. Nature Communications, 11 (1)
Perez, Amilcar J., Cesbron, Yann, Shaw, Sidney L., Bazan Villicana, Jesus, Tsui, Ho-Ching T., Boersma, Michael J., Ye, Ziyun A., Tovpeko, Yanina, Dekker, Cees, Holden, Séamus, Winkler, Malcolm E., 2019. 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, 116 (8), pp. 3211-3220
Sage, Daniel, Pham, Thanh-An, Babcock, Hazen, Lukes, Tomas, Pengo, Thomas, Chao, Jerry, Velmurugan, Ramraj, Herbert, Alex, Agrawal, Anurag, Colabrese, Silvia, Wheeler, Ann, Archetti, Anna, Rieger, Bernd, Ober, Raimund, Hagen, Guy M., Sibarita, Jean-Baptiste, Ries, Jonas, Henriques, Ricardo, Unser, Michael, Holden, Séamus, 2019. Super-resolution fight club: assessment of 2D and 3D single-molecule localization microscopy software. Nature Methods, 16 (5), pp. 387-395
Lambert, Ambroise, Vanhecke, Aster, Archetti, Anna, Holden, Séamus, Schaber, Felix, Pincus, Zachary, Laub, Michael T., Goley, Erin, Manley, Suliana, 2018. Constriction rate modulation can drive cell size control and homeostasis in C. crescentus. iScience, 4, pp. 180-189
Holden, Séamus, 2018. Probing the mechanistic principles of bacterial cell division with super-resolution microscopy. Current Opinion in Microbiology, 43, pp. 84-91
Bisson-Filho, Alexandre W., Hsu, Yen-Pang, Squyres, Georgia R., Kuru, Erkin, Wu, Fabai, Jukes, Calum, Sun, Yingjie, Dekker, Cees, Holden, Séamus, VanNieuwenhze, Michael S., Brun, Yves V., Garner, Ethan C., 2017. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science, 355 (6326), pp. 739-743
Mignolet, Johann, Holden, Séamus, Bergé, Matthieu, Panis, Gaël, Eroglu, Ezgi, Théraulaz, Laurence, Manley, Suliana, Viollier, Patrick H., 2016. Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator. eLife, 5
Holden, Séamus, Sage, Daniel, 2016. Super-resolution fight club. Nature Photonics, 10 (3), pp. 152-153
Bergé, Matthieu, Campagne, Sébastien, Mignolet, Johann, Holden, Séamus, Théraulaz, Laurence, Manley, Suliana, Allain, Frédéric H -T., Viollier, Patrick H., 2016. Modularity and determinants of a (bi-)polarization control system from free-living and obligate intracellular bacteria. eLife, 5
Pengo, T., Holden, Séamus, Manley, S., 2015. PALMsiever : a tool to turn raw data into results for single-molecule localization microscopy. Bioinformatics, 31 (5), pp. 797-798
Muñoz-Barrutia, Arrate, Carlini, Lina, Holden, Séamus, Douglass, Kyle M., Manley, Suliana, 2015. Correction of a depth-dependent lateral distortion in 3D super-resolution imaging. PLoS One, 10 (11)
Min, Junhong, Vonesch, Cédric, Kirshner, Hagai, Carlini, Lina, Olivier, Nicolas, Holden, Séamus, Manley, Suliana, Ye, Jong Chul, Unser, Michael, 2014. FALCON : fast and unbiased reconstruction of high-density super-resolution microscopy data. Scientific Reports, 4 (1)
Holden, Séamus, Pengo, Thomas, Meibom, Karin L., Fernandez Fernandez, Carmen, Collier, Justine, Manley, Suliana, 2014. 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, 111 (12), pp. 4566-4571
Min, Junhong, Holden, Séamus, Carlini, Lina, Unser, Michael, Manley, Suliana, Ye, Jong Chul, 2014. 3D high-density localization microscopy using hybrid astigmatic/ biplane imaging and sparse image reconstruction. Biomedical Optics Express, 5 (11), pp. 3935-3948
Endesfelder, Ulrike, Finan, Kieran, Holden, Séamus, Cook, Peter R., Kapanidis, Achillefs N., Heilemann, Mike, 2013. Multiscale spatial organization of RNA polymerase in Escherichia coli. Biophysical Journal, 105 (1), pp. 172-181
Holden, Séamus, Uphoff, Stephan, Kapanidis, Achillefs N., 2011. DAOSTORM : an algorithm for high- density super-resolution microscopy. Nature Methods, 8 (4), pp. 279-280
Torella, Joseph P., Holden, Séamus, Santoso, Yusdi, Hohlbein, Johannes, Kapanidis, Achillefs N., 2011. Identifying molecular dynamics in single-molecule FRET experiments with burst variance analysis. Biophysical Journal, 100 (6), pp. 1568-1577
Crawford, Robert, Lymperopoulos, Konstantinos, Torella, Joseph P., Heilemann, Mike, Hwang, Ling C., Holden, Séamus, Kapanidis, Achillefs, 2010. Single-molecule DNA biosensors for quantitative transcription factor detection. Biophysical Journal, 98 (3)
Holden, Séamus, Uphoff, Stephan, Hohlbein, Johannes, Yadin, David, Le Reste, Ludovic, Britton, Oliver J., Kapanidis, Achillefs N., 2010. Defining the limits of single-molecule FRET resolution in TIRF microscopy. Biophysical Journal, 99 (9), pp. 3102-3111
Uphoff, Stephan, Holden, Séamus, Le Reste, Ludovic, Periz, Javier, van de Linde, Sebastian, Heilemann, Mike, Kapanidis, Achillefs N., 2010. Monitoring multiple distances within a single molecule using switchable FRET. Nature Methods, 7 (10), pp. 831-836
Lymperopoulos, Konstantinos, Crawford, Robert, Torella, Joseph P., Heilemann, Mike, Hwang, Ling Chin, Holden, Séamus, Kapanidis, Achillefs N., 2010. Single-molecule DNA biosensors for protein and ligand detection. Angewandte Chemie International Edition, 49 (7), pp. 1316-1320
Lymperopoulos, Konstantinos, Crawford, Robert, Torella, Joseph P., Heilemann, Mike, Hwang, Ling Chin, Holden, Séamus, Kapanidis, Achillefs N., 2010. Einzelmolekül-DNA-Biosensoren zur detektion von proteinen und Liganden. Angewandte Chemie International Edition, 122 (7), pp. 1338-1342

Achurra, Paulina, Holden, Séamus, Pengo, Thomas, Manley, Suliana, 2014. Photoactivated localization microscopy for cellular imaging. In Super-Resolution Microscopy Techniques in the Neurosciences, Totowa, NJ, Humana Press, pp. 87-111
Hwang, Ling Chin, Hohlbein, Johannes, Holden, Séamus, Kapanidis, Achillefs N., 2009. Single-Molecule FRET : methods and biological applications. In Hinterdorfer, P.; Oijen, A. (eds.), Handbook of Single-Molecule Biophysics, New York, NY, Springer, pp. 129-163

Hohlbein, Johannes, Diederich, Benedict, Marsikova, Barbora, Reynaud, Emmanuel G., Holden, Séamus, Jahr, Wiebke, Haase, Robert, Prakash, Kirti, 2022. Open microscopy in the life sciences : quo vadis?. Nature Methods, Nature Publishing Group, pp. 1020-1025

Research Projects

Title	Funder	Award start	Award end
Wellcome Trust Discovery Award Application - December 2022	Wellcome Trust	08 Jan 2024	07 Jan 2032
Cell Wall Formation in Rod Shaped Bacteria - BBSRC sLoLa Full Stage - February 2023	BBSRC	01 Mar 2024	31 Jan 2029
Dr Seamus Holden - EVALUATING ELONGASOME TUG OF WAR AS A KEY REGULATOR OF BACTERIAL CELL WALL SYNTHESIS	BBSRC	01 Jan 2023	30 Sep 2025
Grant Transfer Sir Henry Dale Fellowship for Dr Seamus Holden: 'Super-resolving the physical mechanisms of bacterial cell division ' from Newcastle University to Warwick University	Wellcome Trust	01 Jun 2022	31 Aug 2024
Funded by ROYAL SOCIETY Grant Transfer Sir Henry Dale Fellowship for Dr Seamus Holden: 'Super-resolving the physical mechanisms of bacterial cell division ' from Newcastle University to Warwick University	Royal Society	01 Jun 2022	30 Sep 2023

Teaching / Student Supervision

I am happy to receive enquires about PG Research projects in my group, please contact me at the above email address.

Undergraduate research projects

My lab can supervise undergraduate research projects along the following broad research topics:

Bacterial cell division, differentiation and cell wall synthesis

Physics of life and biophysics of single molecules and complexes
Fluorescence microscopy of bacteria - most projects will involve this

I find it most effective for student training and staff time to run group projects where multiple students study different aspects of the same broad question.

Suggested projects

"Sun cream for your microscope"

Last year, we ran a group project called "Sun cream for your microscope" looking at chemical additives which we could use during live cell microscopy of bacteria to reduce phototoxicity (light induced cell damage) and photobleaching (light induced loss of fluorescent dye labels). Each student studied complementary aspects of the problem. We found exciting pilot results that certain chemical additives could strongly reduce photobleaching, which could substantially improve our live cell microscopy experiments, which should help us learn how bacteria grow and divide.

I would be particularly keen to host students interested in continuing this project. There is lots of potential for exciting follow up experiments to further explore this topic, such as experiments to prove and further investigate the photoprotective effect, and proof of concept experiments to demonstrate improved microscopy performance such as single molecule tracking or live cell microscopy. Given the established nature of this project, there is also the possibility that the work performed in this research project could contribute to a publication on this topic.

Group Members

Current Members
Dr Andrew McMahon - PDRA	Dr David Roberts - PDRA	Josh Edwards - 4th year PhD student
Joe Ratcliffe - 1^st year PhD student	Saba Alaghagi - MBio student	Siham Gabow - MBio student, jointly supervised by Chris Rodriguez