Photonic detection of Alzheimer’s disease biomarkers: conformational fingerprinting of blood-based proteins

About the Project

Alzheimer’s disease impacts over 40 million people worldwide, yet diagnosing it early remains one of medicine’s greatest challenges. The disease is driven by the misfolding and aggregation of β-amyloid (Aβ) and tau proteins, both of which circulate in the bloodstream long before symptoms appear. Current blood tests can measure total protein amounts, but not whether they are in harmless (correctly folded) or disease-causing (mis-folded) forms. 

This project will take a transformative approach to this global problem. You will use single-molecule Förster resonance energy transfer (smFRET) and fluorescence correlation spectroscopy (FCS), which represent two of the most powerful techniques in modern biophysics, to watch these proteins fold, misfold and aggregate one molecule at a time. By capturing nanometer-scale structural changes within these biomarkers, you will identify and count rare misfolded forms that are invisible to conventional detection methods. 

Building on these discoveries, you will develop fluorescent biosensors that can accurately report on the structural state of both Aβ and tau in blood samples. These “smart” biosensors will generate unique fluorescent fingerprints in the presence of pathogenic protein structures, offering a potential route towards next-generation diagnostics for dementia. 

As part of this project, you will design and validate fluorescent labelling strategies, use both smFRET and FCS to quantify protein structure and their dynamics, investigate how components of the blood influence protein structure, stability and detectability, and analyse large datasets from human blood using advanced data analysis tools.  

A key highlight of this project is that you will undergo an industrial placement at Exciting Instruments Ltd., a UK-based world leader in single-molecule microscopy development. During this placement, you will gain hands-on experience in cutting-edge instrument design, translational research and commercialisation processes, which are highly valuable skills for both academic and industrial careers. 

You will join a vibrant, interdisciplinary, diverse and supportive research community at the interface of biophysics, neuroscience and molecular diagnostics, with access to state-of-the-art single-molecule detection instruments. You will join a team with expertise in cutting-edge single-molecule biophysics (Quinn Lab; https://sites.google.com/york.ac.uk/quinnlab/; https://www.york.ac.uk/physics-engineering-technology/people/quinn/; https://x.com/Steve_Quinn_Lab), biochemistry and structural biology (Baumann Lab; https://www.york.ac.uk/biology/people/christoph-baumann/) and instrumentation development (Exciting Instruments; https://excitinginstruments.com/). You will also benefit from rapid and frequent access to state-of-the-art facilities in the York Bioscience Technology Facility (https://www.york.ac.uk/biology/technology-facility/). No previous experience in these techniques is necessary and you will receive thorough experimental training. 

As part of the DiMeN DTP, you will also benefit from cohort-based training, professional development workshops, and networking events across the North of England.

This is an exceptional opportunity to apply cutting edge biophysical techniques to one of the biggest challenges in global health, and you will contribute significantly towards new blood-based structural diagnostics for Alzheimer’s disease. 

Informal enquiries should be addressed to Dr Steven Quinn (steven.quinn@york.ac.uk).

Institutional entry requirements for PhD:

This project will suit candidates with backgrounds in physics, biophysics, biochemistry, physical chemistry, molecular biology, or biomedical engineering. Enthusiasm for fluorescence microscopy, data analysis, and interdisciplinary science is essential. Prior lab experience with protein biochemistry or fluorescence techniques is advantageous but not required.

For entry into this PhD programme, you should have, or expect to obtain an MSc degree at 2:1 (or overseas equivalent) or above in a relevant discipline. We will also consider applicants with a BSc degree at 2:1 or above (or overseas equivalent) where sufficient relevant experience can be demonstrated.

If English is not your first language you must provide evidence of your ability. For further details please visit https://www.york.ac.uk/biomedical-research-institute/phd-biomedical-science/.

Industrial partner website link:

https://excitinginstruments.com/

How to apply:

All applications are made via the application form accessed on the DiMeN website at www.dimen.org.uk

Please read the full application guidance on the website before submitting an application. 

For more details, please see the advertisement.

Understanding the Molecular Mechanisms of Protein-Primed Genome Replication in Enteroviruses.

About the Project

Enteroviruses are widespread human pathogens responsible for illnesses ranging from mild respiratory infections to severe neurological and cardiac diseases. This PhD project aims to uncover the structural and mechanistic principles that govern RNA replication in enteroviruses. Using cutting-edge biochemical, structural, and single-molecule biophysical techniques, you will investigate how viral and host proteins assemble on conserved RNA structures to initiate genome synthesis — providing new insights into fundamental viral biology and potential antiviral targets.

Enteroviruses (family Picornaviridae) include poliovirus, coxsackievirus, rhinovirus, and echovirus, and together account for more than one billion infections globally each year. Once inside the host cell, their positive-sense, single-stranded RNA genomes must be replicated by first synthesizing a complementary negative-sense strand prior to positive-sense strand synthesis. This process is initiated by a small viral protein, VPg, in its uridylated form, which serves as a primer for RNA synthesis.

The enterovirus genome is highly structured, and several conserved RNA elements are essential for replication. A cloverleaf structure at the 5′ end acts as a scaffold for replication complex assembly by binding both host poly(rC)-binding protein 2 (PCBP2) and the viral 3CD protein (a precursor of the 3C protease and 3D polymerase). Another key RNA element, the cis-replicative element (cre), acts as the template for VPg uridylation, and also interacts with 3C and 3CD proteins. Recent structures of the cloverleaf, and cloverleaf bound to 3CD have provided some insights into this process, but there is no structural information on the larger cloverleaf-PCBP2-3CD complex, or the cre-3C-3CD complex.

You will explore the structural and mechanistic basis of enterovirus replication complex formation by studying the following RNA–protein assemblies:

• cloverleaf–PCBP2–3CD complex

• cre–3C–3CD complex

Your work will involve:

• In vitro reconstitution and purification of RNA–protein complexes

• Biochemical assays to study VPg uridylation

• Structural biology techniques including X-ray crystallography and cryo-EM

• Single-molecule imaging (TIRF, FRET) to probe RNA conformational dynamics and complex assembly kinetics

• Virology experiments in collaboration with Dr Trevor Sweeney (The Pirbright Institute)

You will join a vibrant, diverse, and highly supportive research environment at the University of York, with access to state-of-the-art research facilities and a collaborative supervisory team offering complementary expertise:

• Protein–RNA biochemistry and structural biology – Hill Lab | Profile | @chillzaa

• Single-molecule biophysics and advanced fluorescence imaging – Quinn Lab | Profile | @Steve_Quinn_Lab

• Molecular biology of protein-primed polymerases – Mukherjee Lab | Profile

You will have frequent access to:

• The York Structural Biology Laboratory (YSBL) for X-ray crystallography and cryo-EM

• The Molecular Interactions Laboratory at the Bioscience Technology Facility

No prior experience in these techniques is required; you will receive comprehensive experimental training across all relevant disciplines.

You should hold, or expect to hold, an honours degree in a related subject area for entry into this PhD programme with a 2:1 or first-class honours (or overseas equivalent). If English is not your first language you must provide evidence of your ability. For further details please visit https://www.york.ac.uk/biomedical-research-institute/phd-biomedical-science/.  

How to apply:

All applications are made via the application form accessed on the DiMeN website at www.dimen.org.uk

Please read the full application guidance on the website before submitting an application. 

For more details, please see the advertisement.

Single-Molecule Fluorescence Detection of Early-Stage Dementia Biomarkers

About the Project

Background: The term dementia covers a range of diseases minimally understood and accepted as incurable therefore impacting financially on health care systems and the community affected. It is an extensive field with only the tip of the iceberg addressed. By the time symptoms are prevalent the disease is so progressed that the outcome is non-reversible. Our project aims to readdress the same questions but with a new approach, a high-level nanotechnology investigation that connects in vitro, in vivo and community. This project is collaborative with a biochemistry/ molecular biology/ biophysics/community impact approach. We will address questions around the structure, dynamics and conformations of these biomarkers. A background and interest in any of the following fields would be advantageous; biochemistry, biophysics, optics, chemistry and molecular biology.

Aim and objectives: Since understanding small biomolecules in vitro will always offer limitations in how this information translates in vivo, a critical angle of our project would be to combine sm FRET studies with an appropriate animal model. Are sub-populations, for example, directly related to how cognitive function decline is seen in vivo? Does understanding dynamics, molecular flexibility as well as conformational change inform on structures more prevalent at certain stages of dementia, allowing us to fully answer questions around early detection in this disease and those related?

The sm fluorescence approach would allow us to answer questions such as: is biomarker mis-folding influenced by local environmental factors? Do biomarkers dynamically fluctuate & over what timescales? Are transient/ mis-folded species neurotoxic? Biomarkers targeted will include Aβ 4.5kDa, Aβ40/Aβ 42 since they are the most abundant & linked to the formation of plaques. Also τ50 kDa, phosphorylated forms, and p-τ217 which has emerged as a strong indicator of amyloid pathology.

The outcomes of this project are to fully understand the structure, dynamics and behaviour of those biomarkers known to be involved in dementia related disease, molecule by molecule. The purpose is to add a level of understanding that can inform drug design and assay development.

Lab websites and links:

Dr. Tara Sabir: http://www.leedsbeckett.ac.uk/staff/dr-tara-sabir/

ORCID ID: https://orcid.org/0000-0002-3268-1344

Dr. Steve Quinn:https://www.york.ac.uk/physics-engineering-technology/people/quinn/

Group webpage: Biological Nanosystems Laboratory - School of Physics, Engineering and Technology, University of York

Dr. Ines Hahn:https://www.york.ac.uk/biology/people/ines-hahn

Group webpage https://sites.google.com/york.ac.uk/hahnlab

For informal enquiries about the project, please contact:

Dr Tara Sabir

Email address [t.sabir@leedsbeckett.ac.uk]

About the BBSRC Yorkshire Bioscience Doctoral Training Partnership (YBDTP):

The YBDTP brings together world-class bioscience research and innovation, as well as excellence in doctoral supervision, across the Yorkshire and Teesside region. The YBDTP will fund postgraduate researchers at the Universities of Leeds, Sheffield, York, Bradford, Huddersfield, Hull, Leeds Beckett, Sheffield Hallam and Teesside forming a strong regional training partnership. In YBDTP you'll benefit from a regional doctoral training programme that has interdisciplinary collaboration at its core. The aim is to enable you to develop a range of research skills in biological, biotechnology and biochemical areas as well as equip you with core data analysis and professional skills that are necessary for bioscience research and related non-academic careers.

https://www.yorkshirebiosciencedtp.ac.uk

Eligibility:

Open to International (including EU) and UK (home) students.

You can apply if you have, or are expecting to gain, at least an upper second-class honours degree or equivalent. Due to the interdisciplinary nature of this programme, we welcome applications if your background is in any biological, chemical or physical science or mathematics and are interested in using your skills in addressing biological questions. International students should check if they meet the entry requirements for the host university.

We aim to support the most outstanding applicants from outside the UK and are able to offer a very limited number of bursaries that will enable full studentships to be awarded to international (EU and non-EU) applicants. These full studentships will only be awarded to exceptional quality candidates, due to the highly competitive nature of this scheme.

The YBDTP is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Not all projects will be funded; a limited number of candidates will be appointed via a competitive process.

English language: If English isn't your first language, you may need to provide evidence of your English language ability. Please see the English language requirements for the host university.

https://www.leedsbeckett.ac.uk/the-graduate-school/research-degrees/faqs/

How to apply:

Application deadline: 5pm (UK time), Wednesday 7th January 2026

For more details, please see the advertisement.

Life pushed to extremes: probing the mechanisms of chromosome segregation in thermophilic Archaea

About the Project

Lead supervisor: Prof Daniela Barillà, University of York

Co-supervisors: Dr Steven Quinn, School of Physics, Engineering and Technology, University of York and Dr George Heath, School of Physics and Astronomy, University of Leeds

The student will be registered with the Department of Biology (University of York)

Life pushed to extremes: probing the mechanisms of chromosome segregation in thermophilic Archaea

Chromosome segregation is a fundamental biological process in all organisms. The genetic material is first duplicated, then separated and equally distributed into the two daughter cells. The mechanisms mediating this cell-cycle event are well characterized in eukaryotes, but they are poorly defined in archaea, the third domain of life.

Archaea evolved as a domain of life billions of years ago, but they are a relatively recent addition to the map of the universal tree of living organisms. Archaea are widely disseminated in the most disparate environmental niches and present unique molecular adaptations to life pushed to extremes. New studies have recently suggested that Eukaryotes originated from Archaea and have casted a novel light on this domain of life.

The project will investigate chromosome segregation in thermophilic archaea whose genome encodes two proteins, SegA and SegB, that interact to form a minimal chromosome segregation machine. SegA is an enzyme that hydrolyses ATP, whereas SegB is a DNA-binding protein that recognises centromere sites on the chromosome. This is the prototype of a DNA partition system widespread across archaea. The main aim is to investigate SegB homologues from different genera. The AlphaFold-predicted structures of these proteins present peculiar Beta-helix, solenoid-like domains, whose function is elusive. The cross-disciplinary approaches to solve this jigsaw involve molecular biology/biochemistry (cloning, protein purification, DNA-protein and lipid-protein assays) in parallel to cutting-edge techniques ranging from optical tweezers to high-speed atomic force microscopy to visualize DNA/lipid binding in real time.

You will be supported by three supervisors. The departments (York & Leeds) host state-of-the-art technology facilities that your research project will benefit from. You will attend several in-house graduate skills training courses and will be offered opportunities to attend scientific conferences. All the supervisors are involved in outreach activities, and you will be encouraged to become involved in these opportunities.

The YBDTP and the University of York are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

The Department of Biology holds an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.

Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions. 

Programme: PhD in Biology (4 years)

Start Date: 21 September 2026

About the Yorkshire Bioscience Doctoral Training Partnership (YBDTP):

The YBDTP brings together world-class bioscience research and innovation, as well as excellence in doctoral supervision, across the Yorkshire and Teesside region. The YBDTP will fund postgraduate researchers at the Universities of Leeds, Sheffield, York, Bradford, Huddersfield, Hull, Leeds Beckett, Sheffield Hallam, and Teesside, forming a strong regional training partnership. In YBDTP you'll benefit from a regional doctoral training programme that has interdisciplinary collaboration at its core. The aim is to enable you to develop a range of research skills in biological, biotechnological, and biochemical areas, as well as equip you with core data analysis and professional skills necessary for bioscience research and related non-academic careers.

How to apply

To be considered for this project, you will need to complete an expression of interest.

You can be considered for a maximum of three YBDTP projects (at the same university or at different universities).

Please note that students who need a visa to study in the UK will NOT be considered for this York project. Other universities that are part of the YBDTP may consider international students. If you have questions about the application process, email YBDTP@leeds.ac.uk

For more details, please see the advertisement.