Post-doc position available

Post-doctoral Reseach Associate, Mechanistic principles of bacterial cell division

Salary: £27,629 – £32,958

Closing date: 14th December 2017

Apply online: http://www.jobs.ac.uk/job/BFT547/research-assistant-associate-a84974r/

We seek an enthusiastic Post-doctoral Research Associate to join our laboratory. This Wellcome Trust funded post is for 3 years and is based at the Centre for Bacterial Cell Biology at Newcastle University.

Our interdisciplinary lab investigates fundamental principles of bacterial cell division and spatial organization. To achieve this, we push the limits of bacterial cell biology by fusing cutting edge microbiology with super-resolution microscopy, microfabrication and microfluidics.

This project will elucidate the functional role of the bacterial cytoskeletal protein FtsZ and associated proteins during Bacillus subtilis cell division by measuring in vivo protein organization and ultrastructure by super-resolution microscopy.

This position would particularly suit bacterial cell biologists with an interest in microscopy, or applicants with other relevant expertise (eg. cytoskeleton specialists). Prior experience in super-resolution microscopy is not required. Applicants should be in possession of, or near finalization of, a PhD in a relevant field.

ICaMB is committed to the Athena SWAN Charter for Women in Science as detailed on our web site (http://www.ncl.ac.uk/camb)

Further information can be obtained by contacting Dr Seamus Holden (seamus.holden@ncl.ac.uk).

Post-doc position in biophysics of bacterial cell division

Start date: mid-2017 (negotiable)
Application deadline: 24th May 2017

Joint position between Holden lab, Newcastle University, UK and Dekker lab, TU Delft, Netherlands.

We have an opening for an outstanding experimental post-doc to pursue an exciting project at the interface of biophysics, microbiology, nanofabrication, and super-resolution microscopy.

In order to divide, bacteria assemble a dynamic multi-protein nanomachine which builds a cross-wall at the middle of the cell. This is a fascinating physical puzzle: how do one of the major branches of life, the bacteria, cut themselves in half for reproduction? It is also medically important: if we can better understand how bacteria divide, we may be able to devise new antibiotics to directly target this process.

The small size of bacteria makes it difficult to study division directly in cells. However, we recently combined super-resolution microscopy with nanofabricated micro-cages which force bacteria to stand on their heads, allowing superb imaging of the cell division plane. Together these advances allow us to study bacterial cell division in real time, at ultra-high resolution directly in cells [1].

In this project, you will unravel basic physical principles of bacterial cell division by further developing this new technology and using it to study how bacteria construct their dividing crosswall, both at the microscale, at the level of the entire crosswall, and at the nanoscale, i.e. at the level of the individual cell-wall building nanomachines.

We are looking for a biophysicist with prior expertise in any of these areas: super-resolution microscopy, single molecule imaging, bacterial biophysics, or nanofabrication. Prior experience in microbiology is not required. Applicants should have an excellent publication record and possess a doctorate by the position start date. The postdoc will work at both Delft (mostly cleanroom microfabrication and basic characterization) and Newcastle (high-resolution imaging).

Please send applications, with CV and references to: seamus.holden@ncl.ac.uk and c.dekker@tudelft.nl

[1] A.W. Bisson-Filho, Y.-P. Hsu, G.R. Squyres, E. Kuru, F. Wu, C. Jukes, Y. Sun, C. Dekker, S. Holden, M.S. VanNieuwenhze, Y.V. Brun, E.C. Garner, Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division, Science. 355 (2017) 739-743. doi:10.1126/science.aak9973.

How a motile cytoskeleton drives bacterial cell division

We just solved a 25 year old mystery: the basic mechanistic principle of bacterial cell division. We found that a motile bacterial cytoskeleton drives the motion of enzymes which build a partition wall across the middle of the cell. In the longer term, this may help us find new antibiotics to target this process.

Animation credit TU Delft / Scixel.

The story has just been published in Science, here.

Newcastle’s press office wrote a great pop science article about the discovery, here.

A big thanks to Calum Jukes, a graduate student in my lab, for all his hard work on this. And to our wonderful collaborators in Harvard, Indiana and Delft on this multi-lab team-up, it’s been a pleasure!

Reference

Alexandre W. Bisson Filho, Yen-Pang Hsu, Georgia R. Squyres, Erkin Kuru, Fabai Wu, Calum Jukes, Yingjie Sun, Cees Dekker, Seamus Holden, Michael S. VanNieuwenhze, Yves V. Brun, and Ethan C. Garner, Treadmilling by FtsZ Filaments Drives Peptidoglycan Synthesis and Bacterial Cell Division. Science. 355 (2017) 739-742. doi:10.1126/science.aak9973.

 

 

2 PhD positions available

There’s still time to apply for two really exciting positions in my lab on the single molecule biology of cell division:

https://www.findaphd.com/search/projectDetails.aspx?PJID=80669&LID=1120
https://www.findaphd.com/search/ProjectDetails.aspx?PJID=80888&LID=3415

Deadlines are very soon – 5th/ 6th January – don’t miss out!

Informal enquiries (with CV) welcome: seamus.holden@ncl.ac.uk

UPDATE: I want to emphasis that prior interdisciplinary expertise is not required! Applications from students with experience in only a single subect, eg pure biology or pure physics, are very welcome.

BBSRC funded PhD position available!

Do you want to join an exciting international collaboration to redefine our understanding of bacterial cell division by combining biophysics, bacterial cell biology, super-resolution microscopy and microtechnology?

– What scientific question will you investigate?
How does a bacterium divide? Not only is this one of the most basic questions we can ask about a living organism, but it is also important for medicine and biosciences, since bacterial cell division is a key antibiotic target. Bacteria divide by building a partition wall along the cell centreline against a high outwards pressure (up to 30 atmospheres!). To achieve this, the cytoskeletal protein “FtsZ” assembles a multi-protein division machine to insert cell wall material at mid-cell.

We recently dramatically improved our understanding of bacterial cell division machinery with our recent discovery (Bisson Filho et al, BioRxiv pre-print 2016)) that bacterial cell division in Bacillus subtilis is carried out by individual cell wall synthesis complexes, driven by the treadmilling motion of the bacterial cytoskeleton. You will work to further define the organization and dynamics of these dynamic synthesis complexes at the single molecule level in living cells, in partnership with a leading team of international collaborators (UK, USA, Netherlands). You will achieve this by applying cutting edge biophysical methods to a fundamental problem in bacterial cell biology: you will use single molecule super-resolution microscopy of live bacteria, combined with microfluidics and microtechnology, to directly observe the motion and organization of individual cell division proteins. This project will reveal for the first time the physical mechanism by which the bacterial cytoskeletal protein FtsZ and cell wall synthesis proteins coordinate their coupled motion.

– What will you be doing for your PhD research?
You will perform highly interdisciplinary work, working on both biophysics/ advanced microscopy and microbiology. This will include using super-resolution microscopy to measure the motion and stoichiometry of divisome proteins at the molecular level, microfluidic perturbation and microstructured immobilization of bacteria, quantitative data analysis, creation and genetic manipulation Bacillus subtilis strains containing fluorescently-labelled cell division proteins, and synthesis of new labelling probes for high resolution microscopy.

– What training will you receive?
You will join an exciting collaboration an exciting multidisciplinary international collaboration of biophysicists/ advanced microscopists (Newcastle, UK), bacterial cell biologists (Harvard, USA), biological chemists (Indiana, USA), nanotechnologists (Delft, Netherlands) and biochemists (Liverpool, UK). You will gain experience of each of these disciplines, with particular focus on “bacterial biophysics”, as well as nanotechnology, building on the key enabling technology which we developed between Newcastle and Delft, using microstructured immobilization to vertically orient bacteria for high resolution imaging.

– Is this project right for you?
We are seeking someone from either the physical or biological sciences with a strong interest in bridging the two disciplines and a good degree (BSc/MSci 2(1) or above, or MSc).
UK students only.

Funding Notes
This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,296 for 2016-17). The PhD will start in October 2017. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.

References
Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. AW Bisson-Filho, YP Hsu, GR Squyres, E Kuru, F Wu, C Jukes, C Dekker#, S Holden#, MS VanNieuwenhze#,3, YV Brun#, and EC Garner#. BioRxiv doi: 10.1101/077560. #Co-corresponding authors.

To apply:
Please submit a full CV and covering letter directly to seamus.holden@ncl.ac.uk
Informal enquiries welcome!

Post-doc position available: Biophysics of bacterial cell division (with Cees Dekker at Delft)

We recently made (in collaboration with several labs) the surprising and very exciting discovery that FtsZ treadmills around mid-cell, and this treadmilling directs and drives cell wall synthesis. (Preprint here).

We now have a postdoc position available to follow up this exciting story, studying the biophysics of bacterial cell division using advanced and single molecule microscopy in a joint project between the labs of Cees Dekker at Delft and my lab at Newcastle. 

Please send applications with CV to seamus.holden@ncl.ac.uk and c.dekker@tudelft.nl. See also http://ceesdekkerlab.tudelft.nl/job-openings/

 

PhD position available: Creating a high-throughput microscopy tool that can determine how antibiotics work

Antibiotic resistance threatens to return us to a pre-antibiotic era, where even minor infections can kill. To avoid this, we need to find new antibiotics with novel “modes of action” (MOAs) that kill bacteria in new ways compared to previous drugs. Antibiotics with novel MOA are harder for bacteria to develop resistance to, so they will be more effective and useful for longer. However, existing methods to determine MOA are slow, expensive and inaccurate.

During this studentship you will tackle this problem using a multidisciplinary approach combining microbiology and engineering. You will develop a high-throughput microscopy method that rapidly and accurately determines MOA by measuring changes in bacterial cell shape and organization. You will:

  • Establish high-throughput microscopy of the bacterium Bacillus subtilis in a multi-well plate/ robotics format, adapting existing low throughput methods.
  • Develop novel algorithms for automated high throughput assessment of MOA based on changes in bacterial cell shape and organization.
  • Screen the natural product extract library of Demuris, a Newcastle University spin-out company, for antimicrobials with unique MOA for further development.

You will receive cutting-edge training in quantitative image analysis, advanced microscopy and bacterial cell biology. Industrial research experience will be gained during a 3-month placement with Demuris.

The studentship is fully funded by the EPSRC and available to UK/ EU nationals.

Full details here: http://www.ncl.ac.uk/postgraduate/funding/sources/ukeustudents/cb122.html. Apply online or send me an informal enquiry (with CV) to seamus.holden@ncl.ac.uk

More details  (the ones that would not fit into the ad space):

Recently, a microscopy based method, “bacterial cytological profiling”, was developed for determining antimicrobial mode of action by measuring changes in bacterial cell shape and internal organization (Nonejuie et al, PNAS 2013). Our goal is to create a high throughput, fully automated version of bacterial cytological profiling, and use it for natural product screening.

Note that a full stipend is available to EU nationals despite the ambiguity in the official advert.

Localization microscopy challenge 2016 launched

Here’s one for all my fellow super-res geeks:

We would like to announce the second edition of Single Molecule Localization Microscopy Challenge at the upcoming SMLMS 2016.

http://bigwww.epfl.ch/smlm/challenge2016/

After the success of the first challenge in 2013, we would like to continue the benchmarking of SMLM software, and to extend the challenge to key unaddressed areas of the field. This challenge will focus on two aspects of localisation microscopy:

– 3D, which despite being one of the most exciting applications of SMLM from day one has seen significantly less algorithm development than 2D

– Ultra High-density 2D intended for live cell applications. The 2D UHD challenge is specifically intended to allow the direct competition of both “localization” methods and image-based methods which do not necessarily resolve individual molecules, such as SOFI, sparse deconvolution and 3B.

We will also be updating the 2013 challenge with additional structures and conditions.

In order to tailor the challenge to the needs of the community, we will open a community consultation of the SMLM challenge 2016 draft specification. You are kindly invited to join the discussion. The consultation will take place via the SMLM challenge discussion group which will also serve as a discussion platform during the rest of the competition: https://groups.google.com/forum/#!forum/lm-challenge-discuss

The draft specification is here: https://docs.google.com/document/d/1cKmKYpkEXu4EeS2AIIcv8nybEb7DUwYkymoK6HDEG1w/pub

The challenge is open to all individuals or teams, academic or corporate, that developed or are currently developing super-resolution software tools and algorithms. We are also open to submissions by expert users of a software.Your participation is important. It will allow the research community to better understand the current state of localization algorithms and software, and to discuss future directions of the field. The challenge is also an excellent platform for exchanging ideas, sharing your experience, and making your software more well-known to the users.

SMLMS 2016 will be the fifth edition of the Single Molecule Localization Microscopy Symposium. It is becoming one of the major event in the field, providing a fruitful platform for engineers and practitioners to interact and collaborate. The conference will be held on 28-30 August 2016 in Lausanne, Switzerland, incorporating a special session for the SMLM challenge: http://smlms.epfl.ch/

Looking forward for your input,

From the organisation committee,

Daniel Sage
Thomas Pengo
Junhong Min
Hagai Kirshner
Bernd Rieger
Ricardo Henriques
Nils Gustafsson
Hazen Babcock
Guy Hagen
Martin Ovesny
Tomas Lukes
Seamus Holden

Phd position available: Super-res + E coli cell division = awesome.

A PhD position, joint between mine and Waldemar Vollmer’s labs is available.

You will use single molecule imaging, one of the hottest and most powerful imaging techniques around, to obtain fundamental and groundbreaking new information about the organization and dynamics of the E coli cell division machine. This will help the fight against antibiotic resistance by informing the search for new cell-division inhibiting antibiotics.

We are looking for talented interdisciplinary scientists from either the physical or biological sciences.

The studentship covers full fees and a stipend for both UK and EU students. Note that findaphd mentions that EU students have to pass an “excellence” threshold to be eligible for the stipend, but you also need to pass this threshold to get the job 😉

Full details and online application at findaphd:
http://www.findaphd.com/search/projectDetails.aspx?PJID=70246

Closing date 22/1/2016.

Publication: Correction of a Depth-Dependent Lateral Distortion in 3D Super-Resolution Imaging

Carlini L*, Holden S*, Douglass K*, Manley S. Correction of a Depth-Dependent Lateral Distortion in 3D Super-Resolution Imaging. PLoS ONE 2015.
*Equal author contribution

Three-dimensional (3D) localization-based super-resolution microscopy (SR) requires correction of aberrations to accurately represent 3D structure. Here we show how a depth-dependent lateral shift in the apparent position of a fluorescent point source, which we term `wobble`, results in warped 3D SR images and provide a software tool to correct this distortion. This system-specific, lateral shift is typically > 80 nm across an axial range of ~ 1 μm. A theoretical analysis based on phase retrieval data from our microscope suggests that the wobble is caused by non-rotationally symmetric phase and amplitude aberrations in the microscope’s pupil function. We then apply our correction to the bacterial cytoskeletal protein FtsZ in live bacteria and demonstrate that the corrected data more accurately represent the true shape of this vertically-oriented ring-like structure. We also include this correction method in a registration procedure for dual-color, 3D SR data and show that it improves target registration error (TRE) at the axial limits over an imaging depth of 1 μm, yielding TRE values of < 20 nm. This work highlights the importance of correcting aberrations in 3D SR to achieve high fidelity between the measurements and the sample.

Carlini-PLoSOne-2015-fig1-scaled

Welcome!

Finally… 5 months post-arrival, a website!

In the Holden lab, we study biophysics in bacteria, especially bacterial cell division, using super-resolution microscopy. We are based at the Centre for Bacterial Cell Biology at the University of Newcastle.

Currently we are microscope building and getting the hang of our new favourite model organism, Bacillus subtilis (pictured in the header). Watch this space for new developments.