Openings

Openings for two fully funded PhDs and a CSC Scholarship proposal

Applications close in January!

Investigation of protein-protein interactions that regulate RNA processing in the nucleus using novel super-resolution microscopy

Please get in touch so we can advise you how to make a strong application.

Deadline: 11 January 2021
LSI Studentship
Funding: Places are fully funded with funding also available for overseas applicants. This includes payment of tuition fees, a personal stipend for 3.5 years (currently £15,009 per year 2019/20) and a training budget
Start date: September 2021
How to Apply: Online Application via Exeter Website

The project is a collaboration between the Soeller lab and the West lab at the Living Systems Institute.

Nucleus condensates

In this project we will use new super-resolution imaging methods to observe mechanisms of RNA transcription – one of the most fundamental processes in Cell Biology. Most transcription is carried out by RNA polymerase II (Pol II) but much of what we know about this comes from indirect experiments as we have been historically unable to directly observe the processes taking place. One of our major research interests is the mechanism by which transcription terminates in a process essential for genome punctuation. Recent work has revealed the fundamental role of so called "protein condensates" that locally concentrate RNA processing proteins in tiny regions within the nucleus. We will study these condensates using the new protein-protein interaction imaging methods that we have recently developed to see how they are formed and regulated in situ. The images on the left, obtained in our laboratories, show these condensates where molecular clusters of Pol II are concentrated. In addition to its fundamental importance, many of the processes and factors implicated in RNA processing are mis-regulated in diseases including cancer and neurodegenerative disorders. This is an exciting opportunity at the interface of Biophysics and Molecular Biology.

The student will receive training in advanced super-resolution miscroscopy, 'big data' analysis, mammalian cell culture, biophysics and RNA biology.

This studentship is part of the LSI doctoral program. The LSI provides a unique training program by housing world-leading Biologists, Physicists, Mathematicians, Computational Scientists and Engineers using cutting-edge technologies. The LSI's mission is to understand life across all scales - from individual atoms to whole organisms - and to discover approaches for improving health and treating disease. For this program we wish to recruit the best and most imaginative students from across the full range of disciplines to join our thriving community of over 60 PhD students.

3D super-resolution probing of DNA nanostructures using deep learning

Deadline: 25 January 2021
EPSRC Studentship
Funding: Places are fully funded with funding also available for overseas applicants. This includes payment of tuition fees, a personal stipend for 3.5 years (currently £15,009 per year 2019/20)
Start date: September 2021
How to Apply: Online Application via Exeter Website

Recently it has become possible to design and make intricate 3D synthetic nanostructures. This is the basis of a revolution in material science as well as new drug designs and delivery methods to mention just a few applications.

In this project we will design and make intricate 3D nanostructures from DNA that we design on the computer and build in the test tube, so called DNA origami. We will collaborate with DNA nanotechnology chemists from Imperial College with whom we have a longstanding collaboration to design and synthesise the DNA origami structures.

DNA origami

A major challenge has been the characterisation of such purpose designed structures to ensure that they are indeed folded in 3D as designed on the computer. Furthermore, the flexibility and rigidity at the molecular level is a major focus to give these nanostructures the mechanical properties that make them useful in applications. To address this challenge we will use new optical imaging techniques, so called optical super-resolution, that will allow us to directly take molecular scale images of the 3D DNA origami structures with a resolution that is better than 10 nm. This will also allow us to probe the flexibility of these structures when we mechanically load them.

An important aspect of the imaging of these nanostructures will be the use of deep learning methods to analyse the image data and help us construct even higher resolution images of these synthetic nanostructures. We will implement a number of existing deep learning approaches that have recently been introduced and train them with our data to provide analysis with previously unattaianble spatial and temporal resolution.

The insights of the 3D DNA origami design and synthesis will be used to implement and validate molecular scale biological imaging aplications that, for example, can monitor at the molecular scale how a virus enters a cell.

The student will receive training in advanced super-resolution miscroscopy, DNA nanotechnology, deep learning and application of DNA structures for biological imaging.

New super-resolution imaging techniques to study protein-protein interactions underlying RNA transcriptional control

Deadline: 11 January 2021
China Scholarship Council (CSC) full-time PhD scholarships hosted at the LSI

The Living Systems Institute (LSI) offers research projects for full-time PhD scholarships in collaboration with the China Scholarship Council (CSC). These studentship opportunities are for the September 2021 intake.

The proposed project would be jointly hosted by the Soeller lab and the West lab at the Living Systems Institute.

The project builds on new DNA based biological super-resolution imaging tools that we recently established [1,2,3] and a BBSRC funded project "A new super-resolution proximity assay to probe RNA transcription condensates".

If you are interested in this or a similar project, please contact us (email C.Soeller@exeter.ac.uk) well in advance of the deadline (midnight on 11 January 2021).

References

  1. Alexander H Clowsley, William T Kaufhold, Tobias Lutz, Anna Meletiou, Lorenzo Di Michele, Christian Soeller. Detecting nanoscale distribution of protein pairs by proximity dependent super-resolution microscopy (2020), Journal of the American Chemical Society.

  2. Alexander H. Clowsley, William T. Kaufhold, Tobias Lutz, Anna Meletiou, Lorenzo Di Michele, Christian Soeller. Repeat DNA-PAINT suppresses background and non-specific signals in optical nanoscopy (2020), bioRxiv, 2020.04.24.059410. (now in press at Nature Communications).

  3. Phil Szuromi. Holding protein pairs in place (2020), Science, 369:155-156.

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