Bill Söderström is interested in how bacterial cells go about dividing. He is also curious about how cell shape influences infection and how cells may use ‘shape-shifting’ to fool the human immune system. He investigates this by using advanced imaging techniques in combination with microfluidic-based approaches. The overall goal of Bill’s research is to get a better understanding of how bacteria divide and behave during infection. In this way, he wants to develop ways to inhibit division, with the rationale that if cells cannot divide, they cannot spread infection.
Bill obtained his doctoral degree in Biophysics at Stockholm University in 2014 under the joint supervision of Profs. Gunnar von Heijne and Daniel Daley. There he worked on the timing and subcellular architecture of the bacterial division machinery, the divisome, and its main regulator, FtsZ.
He later took up a postdoctoral scholar position at the Okinawa Institute of Science and Technology (OIST) in Japan, to further study bacterial cell division. At OIST he developed approaches in Correlative cryo-Light and cryo-Electron Microscopy (Cryo-CLEM) to obtain new information about protein localization during division. He also pioneered ways to image bacteria in a vertical position using micron holes, that in combination with super-resolution fluorescence microscopy, provide superior resolution of the full division ring in one go.
His work on these topics has received multiple recommendations in the Faculty of 1000, been mentioned in popular media and is regularly highlighted in review articles.
Bill also holds a Master of Science in Engineering Physics from the Royal Institute of Technology, KTH, in an interdisciplinary program with the Karolinska Institute (KI), both in Stockholm, Sweden. He focused on understanding the physics of medical imaging systems such as Positron Emission Tomography (PET), Magnetic Resonance Imagining (MRI) and Ultrasound.
In December 2019, he joined UTS and the ithree institute and is currently developing his independent research focusing on bacterial morphology and how pathogenic bacteria use ‘shape-shifting’ to evade the human immune response during urinary tract infection (UTI).
Can supervise: YES
· Super-resolution fluorescence microscopy.
· Microfluidics engineering.
· Bacterial cell division and morphology.
· Infection biology; urinary tract infections.
Chan, H, Soderstrom, B & Skoglund, U 2020, 'Spo0J and SMC are required for normal chromosome segregation in Staphylococcus aureus', MICROBIOLOGYOPEN, vol. 9, no. 4.View/Download from: Publisher's site
Funari, R, Ripa, R, Söderström, B, Skoglund, U & Shen, AQ 2019, 'Detecting Gold Biomineralization by Delftia acidovorans Biofilms on a Quartz Crystal Microbalance', ACS Sensors, vol. 4, no. 11, pp. 3023-3033.View/Download from: Publisher's site
Monterroso, B, Zorrilla, S, Sobrinos-Sanguino, M, Robles-Ramos, MÁ, Alfonso, C, Söderström, B, Meiresonne, NY, Verheul, J, den Blaauwen, T & Rivas, G 2019, 'The Bacterial DNA Binding Protein MatP Involved in Linking the Nucleoid Terminal Domain to the Divisome at Midcell Interacts with Lipid Membranes.', mBio, vol. 10, no. 3.View/Download from: Publisher's site
Division ring formation at midcell is controlled by various mechanisms in Escherichia coli, one of them being the linkage between the chromosomal Ter macrodomain and the Z-ring mediated by MatP, a DNA binding protein that organizes this macrodomain and contributes to the prevention of premature chromosome segregation. Here we show that, during cell division, just before splitting the daughter cells, MatP seems to localize close to the cytoplasmic membrane, suggesting that this protein might interact with lipids. To test this hypothesis, we investigated MatP interaction with lipids in vitro We found that, when encapsulated inside vesicles and microdroplets generated by microfluidics, MatP accumulates at phospholipid bilayers and monolayers matching the lipid composition in the E. coli inner membrane. MatP binding to lipids was independently confirmed using lipid-coated microbeads and biolayer interferometry assays, which suggested that the recognition is mainly hydrophobic. Interaction of MatP with the lipid membranes also occurs in the presence of the DNA sequences specifically targeted by the protein, but there is no evidence of ternary membrane/protein/DNA complexes. We propose that the association of MatP with lipids may modulate its spatiotemporal localization and its recognition of other ligands.IMPORTANCE The division of an E. coli cell into two daughter cells with equal genomic information and similar size requires duplication and segregation of the chromosome and subsequent scission of the envelope by a protein ring, the Z-ring. MatP is a DNA binding protein that contributes both to the positioning of the Z-ring at midcell and the temporal control of nucleoid segregation. Our integrated in vivo and in vitro analysis provides evidence that MatP can interact with lipid membranes reproducing the phospholipid mixture in the E. coli inner membrane, without concomitant recruitment of the short DNA sequences specifically targeted by MatP. This observation strong...
Palmer, SR, Ren, Z, Hwang, G, Liu, Y, Combs, A, Soderstrom, B, Vasquez, PL, Khosravi, Y, Brady, LJ, Koo, H & Stoodley, P 2019, 'Streptococcus mutans yidC1 and yidC2 Impact Cell Envelope Biogenesis, the Biofilm Matrix, and Biofilm Biophysical Properties', JOURNAL OF BACTERIOLOGY, vol. 201, no. 1.View/Download from: Publisher's site
Soderstrom, B, Chan, H & Daley, DO 2019, 'Super-resolution images of peptidoglycan remodelling enzymes at the division site of Escherichia coli.', Current genetics, vol. 65, no. 1, pp. 99-101.View/Download from: Publisher's site
Bacterial cells need to divide. This process requires more than 30 different proteins, which gather at the division site. It is widely assumed that these proteins assemble into a macromolecular complex (the divisome), but capturing the molecular layout of this complex has proven elusive. Super-resolution microscopy can provide spatial information, down to a few tens of nanometers, about how the division proteins assemble into complexes and how their activities are co-ordinated. Herein we provide insight into recent work from our laboratories, where we used super-resolution gSTED nanoscopy to explore the molecular organization of FtsZ, FtsI and FtsN. The resulting images show that all three proteins form discrete densities organised in patchy pseudo-rings at the division site. Significantly, two-colour imaging highlighted a radial separation between FtsZ and FtsN, indicating that there is more than one type of macromolecular complex operating during division. These data provide a first glimpse into the spatial organisation of PG-synthesising enzymes during division in Gram-negative bacteria.
Funari, R, Bhalla, N, Chu, K-Y, Soderstrom, B & Shen, AQ 2018, 'Nanoplasmonics for Real-Time and Label-Free Monitoring of Microbial Biofilm Formation', ACS SENSORS, vol. 3, no. 8, pp. 1499-1509.View/Download from: Publisher's site
Abstract The FtsZ protein is a key regulator of bacterial cell division. It has been implicated in acting as a scaffolding protein for other division proteins, being a force generator during constriction, and more recently, as an active regulator of septal cell wall production. During an early stage of the division cycle, FtsZ assembles into a heterogeneous structure coined the “Z-ring” due to its resemblance to a ring confined by the midcell geometry. While in vitro experiments on supported lipid bilayers have shown that purified FtsZ can self-organize into a swirling ring roughly the diameter of a bacterial cell, it is not known how, and if, membrane curvature affects FtsZ assembly and dynamics in vivo . To establish a framework for examining geometrical influences on proper Z-ring assembly and dynamics, we sculptured Escherichia coli cells into unnatural shapes, such as squares and hearts, using division- and cell wall-specific inhibitors in a micro fabrication scheme. This approach allowed us to examine FtsZ behavior in engineered “Z-squares” and “Z-hearts”, and in giant cells up to 50 times their normal volume. Quantification of super-resolution STimulated Emission Depletion (STED) nanoscopy data showed that FtsZ densities in sculptured cells maintained the same dimensions as their wild-type counterparts. Additionally, time-resolved fluorescence measurements revealed that FtsZ dynamics were generally conserved in a wide range of cell shapes. Based on our results, we conclude that the underlying membrane environment is not a deciding factor for FtsZ filament maintenance and treadmilling in vivo .
Soderstrom, B, Badrutdinov, A, Chan, H & Skoglund, U 2018, 'Cell shape-independent FtsZ dynamics in synthetically remodeled bacterial cells', NATURE COMMUNICATIONS, vol. 9.View/Download from: Publisher's site
Soderstrom, B, Chan, H, Shilling, PJ, Skoglund, U & Daley, DO 2018, 'Spatial separation of FtsZ and FtsN during cell division', MOLECULAR MICROBIOLOGY, vol. 107, no. 3, pp. 387-401.View/Download from: Publisher's site
Soederstroem, B & Daley, DO 2017, 'The bacterial divisome: more than a ring?', CURRENT GENETICS, vol. 63, no. 2, pp. 161-164.View/Download from: Publisher's site
Daley, DO, Skoglund, U & Soederstroem, B 2016, 'FtsZ does not initiate membrane constriction at the onset of division', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Soderstrom, B, Mirzadeh, K, Toddo, S, von Heijne, G, Skoglund, U & Daley, DO 2016, 'Coordinated disassembly of the divisome complex in Escherichia coli', MOLECULAR MICROBIOLOGY, vol. 101, no. 3, pp. 425-438.View/Download from: Publisher's site
Hjelm, A, Soderstrom, B, Vikstrom, D, Jong, WSP, Luirink, J & de Gier, J-W 2015, 'Autotransporter-Based Antigen Display in Bacterial Ghosts', APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 81, no. 2, pp. 726-735.View/Download from: Publisher's site
Soderstrom, B, Skoog, K, Blom, H, Weiss, DS, von Heijne, G & Daley, DO 2014, 'Disassembly of the divisome in Escherichia coli: evidence that FtsZ dissociates before compartmentalization', MOLECULAR MICROBIOLOGY, vol. 92, no. 1, pp. 1-9.View/Download from: Publisher's site
Skoog, K, Soderstrom, B, Widengren, J, von Heijne, G & Daley, DO 2012, 'Sequential Closure of the Cytoplasm and Then the Periplasm during Cell Division in Escherichia coli', JOURNAL OF BACTERIOLOGY, vol. 194, no. 3, pp. 584-586.View/Download from: Publisher's site
McCausland, J, Yang, X, Lyu, Z, Söderström, B, Xiao, J & Liu, J 2019, 'Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism'.
Abstract FtsZ, a highly conserved bacterial tubulin GTPase homolog, is a central component of the cell division machinery in nearly all walled bacteria. FtsZ polymerizes at the future division site and recruits > 30 proteins that assemble into a macromolecular complex termed divisome. Many of these divisome proteins are involved in septal cell wall peptidoglycan (sPG) synthesis. Recent studies found that FtsZ polymers undergo GTP hydrolysis-coupled treadmilling dynamics along the septum circumference of dividing cells, which drives processive movements of sPG synthesis enzymes. The mechanism of FtsZ treadmilling-driven directional transport of sPG enzymes and its precise role in bacterial cell division are unknown. Combining theoretical modeling and experimental testing, we show that FtsZ treadmilling drives the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism, where the shrinking end of FtsZ polymers introduces an asymmetry to rectify diffusions of single enzyme molecules into persistent end-tracking movement. Furthermore, we show that processivity of this directional movement hinges on the balance between the enzyme’s diffusion and FtsZ’s treadmilling speed, which provides a mechanism to control the level of available enzymes for active sPG synthesis, explaining the distinct roles of FtsZ treadmilling in modulating cell wall constriction rate observed in different bacterial species.