Professor Seamus Holden

Professor of Microbial Biophysics

Email: seamus.holden@warwick.ac.uk

Phone: 024 765 75794

Office: IBRB2.28

Bluesky: @seamusholden.bsky.social

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 and Phill Stansfeld at Warwick, as well as colleagues in Belfast, Newcastle, Cambridge, London, Germany, 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.

SLS Y3 undergraduate research projects

See "Teaching/ Student supervision" tab below for detailed description of this year's available Y3 research project .

Staff

We do not have any vacancies currently advertised but we are always happy to host fellowship applications for schemes such as Marie Skłodowska-Curie Fellowships, EMBO LTF, Wellcome ECA.

PhD and Masters students

We are happy to recruit PhD students via either the BBSRC MIBTP programme or the Warwick MRC DTP programme. We 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, chemistry, physics, computer science or engineering.

Undergraduate summer projects

I am happy to supervise talented and self-motivated undergraduate students from any relevant training background who are looking to gain research experience through a summer project. Warwick students can access funding via the URSS scheme. A range of bursary schemes for summer projects are available from learned societies such as the Microbiology Society or the Biochemical Society.

Biography

2024: Promoted to Professor, University of Warwick
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

Benn, Georgina, Bortolini, Christian, Roberts, David M., Pyne, Alice L. B., Holden, Séamus and Hoogenboom, Bart W. (2024) Complement-mediated killing of Escherichia coli by mechanical destabilization of the cell envelope. The EMBO Journal . doi:10.1038/s44318-024-00266-3 ISSN 0261-4189. (In Press)

Vanhille-Campos, Christian, Whitley, Kevin D., Radler, Philipp, Loose, Martin, Holden, Séamus and Šarić, Anđela (2024) Self-organization of mortal filaments and its role in bacterial division ring formation. Nature Physics, 20 . pp. 1670-1678. doi:10.1038/s41567-024-02597-8 ISSN 1745-2473.

Middlemiss, Stuart, Blandenet, Matthieu, Roberts, David M., McMahon, Andrew, Grimshaw, James, Edwards, Joshua M., Sun, Zikai, Whitley, Kevin D., Blu, Thierry, Strahl, Henrik and Holden, Séamus (2024) Molecular motor tug-of-war regulates elongasome cell wall synthesis dynamics in Bacillus subtilis. Nature Communications, 15 (1). 5411. doi:10.1038/s41467-024-49785-x ISSN 2041-1723.

Whitley, Kevin D., Grimshaw, James, Roberts, David M., Karinou, Eleni, Stansfeld, Phillip J. and Holden, Séamus (2024) Peptidoglycan synthesis drives a single population of septal cell wall synthases during division in Bacillus subtilis. Nature Microbiology, 9 . pp. 1064-1074. doi:10.1038/s41564-024-01650-9 ISSN 2058-5276.

Hohlbein, Johannes, Diederich, Benedict, Marsikova, Barbora, Reynaud, Emmanuel G., Holden, Séamus, Jahr, Wiebke, Haase, Robert and Prakash, Kirti (2022) Open microscopy in the life sciences : quo vadis? Nature Methods, 19 . pp. 1020-1025. ISSN 1548-7091 doi:10.1038/s41592-022-01602-3

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 and Henriques, Ricardo (2022) DeepBacs for multi-task bacterial image analysis using open-source deep learning approaches. Communications Biology, 5 . 688. doi:10.1038/s42003-022-03634-z ISSN 2399-3642.

Whitley, Kevin D., Middlemiss, Stuart, Jukes, Calum, Dekker, Cees and 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. doi:10.1038/s41596-021-00668-1 ISSN 1750-2799.

von Chamier, Lucas, Laine, Romain F., Jukkala, Johanna, Spahn, Christoph, Krentzel, Daniel, Nehme, Elias, Lerche, Martina, Hernández-Pérez, Sara, Mattila, Pieta K., Karinou, Eleni et al.

(2021) Democratising deep learning for microscopy with ZeroCostDL4Mic. Nature Communications, 12 (1). 2276 . doi:10.1038/s41467-021-22518-0 ISSN 2041-1723.

Whitley, Kevin D., Jukes, Calum, Tregidgo, Nicholas, Karinou, Eleni, Almada, Pedro, Cesbron, Yann, Henriques, Ricardo, Dekker, Cees and Holden, Séamus (2021) FtsZ treadmilling is essential for Z-ring condensation and septal constriction initiation in Bacillus subtilis cell division. Nature Communications, 12 (1). 2448 . doi:10.1038/s41467-021-22526-0 ISSN 2041-1723.

Wu, Ling Juan, Lee, Seoungjun, Park, Sungshic, Eland, Lucy E., Wipat, Anil, Holden, Séamus and Errington, Jeff (2020) Geometric principles underlying the proliferation of a model cell system. Nature Communications, 11 (1). 4149 . doi:10.1038/s41467-020-17988-7 ISSN 2041-1723.

Sage, Daniel, Pham, Thanh-An, Babcock, Hazen, Lukes, Tomas, Pengo, Thomas, Chao, Jerry, Velmurugan, Ramraj, Herbert, Alex, Agrawal, Anurag, Colabrese, Silvia et al.

(2019) Super-resolution fight club: assessment of 2D and 3D single-molecule localization microscopy software. Nature Methods, 16 (5). pp. 387-395. doi:10.1038/s41592-019-0364-4 ISSN 1548-7091.

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 and 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. doi:10.1073/pnas.1816018116 ISSN 0027-8424.

Lambert, Ambroise, Vanhecke, Aster, Archetti, Anna, Holden, Séamus, Schaber, Felix, Pincus, Zachary, Laub, Michael T., Goley, Erin and Manley, Suliana (2018) Constriction rate modulation can drive cell size control and homeostasis in C. crescentus. iScience, 4 . pp. 180-189. doi:10.1016/j.isci.2018.05.020 ISSN 2589-0042.

Holden, Séamus (2018) Probing the mechanistic principles of bacterial cell division with super-resolution microscopy. Current Opinion in Microbiology, 43 . pp. 84-91. doi:10.1016/j.mib.2017.12.005 ISSN 1369-5274.

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. and Garner, Ethan C. (2017) Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science, 355 (6326). pp. 739-743. doi:10.1126/science.aak9973 ISSN 0036-8075.

Mignolet, Johann, Holden, Séamus, Bergé, Matthieu, Panis, Gaël, Eroglu, Ezgi, Théraulaz, Laurence, Manley, Suliana and Viollier, Patrick H. (2016) Functional dichotomy and distinct nanoscale assemblies of a cell cycle-controlled bipolar zinc-finger regulator. eLife, 5 . e18647. doi:10.7554/eLife.18647 ISSN 2050-084X.

Bergé, Matthieu, Campagne, Sébastien, Mignolet, Johann, Holden, Séamus, Théraulaz, Laurence, Manley, Suliana, Allain, Frédéric H -T. and Viollier, Patrick H. (2016) Modularity and determinants of a (bi-)polarization control system from free-living and obligate intracellular bacteria. eLife, 5 . e20640. doi:10.7554/eLife.20640 ISSN 2050-084X.

Holden, Séamus and Sage, Daniel (2016) Super-resolution fight club. Nature Photonics, 10 (3). pp. 152-153. doi:10.1038/nphoton.2016.22 ISSN 1749-4885.

Muñoz-Barrutia, Arrate, Carlini, Lina, Holden, Séamus, Douglass, Kyle M. and Manley, Suliana (2015) Correction of a depth-dependent lateral distortion in 3D super-resolution imaging. PLoS One, 10 (11). e0142949. doi:10.1371/journal.pone.0142949 ISSN 1932-6203.

Pengo, T., Holden, Séamus and Manley, S. (2015) PALMsiever : a tool to turn raw data into results for single-molecule localization microscopy. Bioinformatics, 31 (5). pp. 797-798. doi:10.1093/bioinformatics/btu720 ISSN 1367-4803.

Min, Junhong, Holden, Séamus, Carlini, Lina, Unser, Michael, Manley, Suliana and 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. doi:10.1364/BOE.5.003935 ISSN 2156-7085.

Min, Junhong, Vonesch, Cédric, Kirshner, Hagai, Carlini, Lina, Olivier, Nicolas, Holden, Séamus, Manley, Suliana, Ye, Jong Chul and Unser, Michael (2014) FALCON : fast and unbiased reconstruction of high-density super-resolution microscopy data. Scientific Reports, 4 (1). 4577 . doi:10.1038/srep04577 ISSN 2045-2322.

Holden, Séamus, Pengo, Thomas, Meibom, Karin L., Fernandez Fernandez, Carmen, Collier, Justine and 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. doi:10.1073/pnas.1313368111 ISSN 0027-8424.

Achurra, Paulina, Holden, Séamus, Pengo, Thomas and Manley, Suliana (2014) Photoactivated localization microscopy for cellular imaging. In: Super-Resolution Microscopy Techniques in the Neurosciences. Neuromethods, 86 . Totowa, NJ: Humana Press, pp. 87-111. ISBN 9781627039826

Endesfelder, Ulrike, Finan, Kieran, Holden, Séamus, Cook, Peter R., Kapanidis, Achillefs N. and Heilemann, Mike (2013) Multiscale spatial organization of RNA polymerase in Escherichia coli. Biophysical Journal, 105 (1). pp. 172-181. doi:10.1016/j.bpj.2013.05.048 ISSN 0006-3495.

Holden, Séamus, Uphoff, Stephan and Kapanidis, Achillefs N. (2011) DAOSTORM : an algorithm for high- density super-resolution microscopy. Nature Methods, 8 (4). pp. 279-280. doi:10.1038/nmeth0411-279 ISSN 1548-7091.

Torella, Joseph P., Holden, Séamus, Santoso, Yusdi, Hohlbein, Johannes and Kapanidis, Achillefs N. (2011) Identifying molecular dynamics in single-molecule FRET experiments with burst variance analysis. Biophysical Journal, 100 (6). pp. 1568-1577. doi:10.1016/j.bpj.2011.01.066 ISSN 0006-3495.

Holden, Séamus, Uphoff, Stephan, Hohlbein, Johannes, Yadin, David, Le Reste, Ludovic, Britton, Oliver J. and Kapanidis, Achillefs N. (2010) Defining the limits of single-molecule FRET resolution in TIRF microscopy. Biophysical Journal, 99 (9). pp. 3102-3111. doi:10.1016/j.bpj.2010.09.005 ISSN 0006-3495.

Uphoff, Stephan, Holden, Séamus, Le Reste, Ludovic, Periz, Javier, van de Linde, Sebastian, Heilemann, Mike and Kapanidis, Achillefs N. (2010) Monitoring multiple distances within a single molecule using switchable FRET. Nature Methods, 7 (10). pp. 831-836. doi:10.1038/nmeth.1502 ISSN 1548-7091.

Lymperopoulos, Konstantinos, Crawford, Robert, Torella, Joseph P., Heilemann, Mike, Hwang, Ling Chin, Holden, Séamus and Kapanidis, Achillefs N. (2010) Einzelmolekül-DNA-Biosensoren zur detektion von proteinen und Liganden. Angewandte Chemie International Edition, 122 (7). pp. 1338-1342. doi:10.1002/ange.200904597 ISSN 1433-7851.

Lymperopoulos, Konstantinos, Crawford, Robert, Torella, Joseph P., Heilemann, Mike, Hwang, Ling Chin, Holden, Séamus and Kapanidis, Achillefs N. (2010) Single-molecule DNA biosensors for protein and ligand detection. Angewandte Chemie International Edition, 49 (7). pp. 1316-1320. doi:10.1002/anie.200904597 ISSN 1433-7851.

Crawford, Robert, Lymperopoulos, Konstantinos, Torella, Joseph P., Heilemann, Mike, Hwang, Ling C., Holden, Séamus and Kapanidis, Achillefs (2010) Single-molecule DNA biosensors for quantitative transcription factor detection. Biophysical Journal, 98 (3). 611a. doi:10.1016/j.bpj.2009.12.3333 ISSN 0006-3495.

Hwang, Ling Chin, Hohlbein, Johannes, Holden, Séamus and Kapanidis, Achillefs N. (2009) Single-Molecule FRET : methods and biological applications. In: Hinterdorfer, P. and Oijen, A., (eds.) Handbook of Single-Molecule Biophysics. New York, NY: Springer, pp. 129-163. ISBN 9780387764962

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.

Year 3 undergraduate research projects

Year 3 projects in my lab will broadly involve the following:

Bacterial cell envelope remodelling, such as bacterial cell division or elongation

Quantitative fluorescence microscopy and single molecule fluorescence microscopy
Molecular microbiology and bacterial genetics

These projects are suitable for students on the School of Life Sciences Biological Sciences, Biochemistry and Biomedical Science degrees. These projects will be wet, ie. involving a mix of laboratory experiments and quantitative data analysis. 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.

2024/25 project: "Single molecule biology of Bacillus subtilis cell wall remodelling"

Bacterial cell wall remodelling is essential for bacterial survival and is one of the best targets for both current and next-generation antimicrobials. Bacillus subtilis is the principal Gram-positive model organism and one of the best models to understand bacterial cell wall remodelling due to its unparalleled genetic tractability.

You will investigate how knockouts or depletions of genes important for cell wall remodelling affect B. subtilis cell elongation or cell division. You will each select one or a few genes of interest from a comprehensive knockout library of all non-essential genes, or a CRISPRi knockdown library of all essential genes. You will characterise the morphological phenotype (ie how cell shape is affected) of these mutants by quantitative fluorescence microscopy. You will then transform mutant strains with DNA coding for either a fluorescent fusion to PBP2B (a cell division protein) or MreB (a cell elongation protein), and look at the cellular localization of these proteins in the mutants. Finally you will perform single molecule tracking of PBP2B or MreB motion in live bacteria to see how deletion/ depletion of the genes of interest affect the processive synthesis carried out by individual divisome or elongasome machines.

To get an idea of what single molecule tracking of bacterial cell wall synthesis proteins looks like, please consult Whitley et al., Nature Microbiology (2024), or Middlemiss et al., Nature Communications (2024).

Group Members

Current Members
Dr Andrew McMahon - PDRA	Dr David Roberts - PDRA	Josh Edwards - PDRA
Joe Ratcliffe - PhD student	Saba Alaghagi - PhD student	Dr Bhuphinder Singh - Senior Research Technician
Dr Jyotsana Parmar - Visiting scientist	Dr Simone Coppola - PDRA	Maria Delgado - MBio student