MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU):

The MRC PPU is one of the world's most renowned centres for research on protein phosphorylation and ubiquitylation (http://www.ppu.mrc.ac.uk/). Many world-leading researchers in the field of signal transduction have trained within the MRC PPU. The major aims of the MRC PPU are to advance understanding of the role of protein phosphorylation and ubiquitylation in cell regulation and human disease, to facilitate the development of drugs to treat diseases caused by abnormalities in phosphorylation, to generate reagents and improve technologies. A key remit of the MRC PPU is to train the next generation of scientists who will advance our understanding in this crucial area of medical research.

Faculty of Life Sciences (FLS):

The MRC PPU is based within the Faculty of Life Sciences at the University of Dundee, a world-class academic institution with a reputation for the excellence of its research, its high-quality teaching and student experience, and the strong impact of its activities outside academia. With 900 staff from over 60 countries worldwide the Faculty provides a dynamic, multi-national, collegiate and diverse environment with state-of-the-art laboratory, technology and teaching facilities.

Michael J Fox Foundation-LRRK2 Investigative Therapeutic Exchange (MJFF LITE) Initiative:

This post will contribute to a highly collaborative Parkinson’s disease research programme sponsored by the MJFF and led by the University of Dundee, that aims to accelerate the development of improved treatments and biomarkers for Parkinson’s disease. Bringing together academic, clinical, biotech and pharmaceutical partners, the programme combines shared chemical tools, advanced laboratory models, patient samples and open data to understand LRRK2 biology, test diverse therapeutic approaches, and identify biomarkers that can guide future clinical trials. By integrating advanced mass spectrometry with cellular, biochemical and clinical-sample approaches, we aim to define how pathogenic LRRK2 variants drive Parkinson’s disease, identify and validate robust biomarkers of pathway activity, and develop and test strategies for earlier diagnosis and more effective treatments.

Position:

We are recruiting for an exceptional, experienced mass spectrometry researcher to join us as a Postdoctoral Researcher within the laboratory of Dario Alessi in the MRC PPU, to run and analyse mass spectrometry experiments defining the role of LRRK2 in Parkinson's disease biology. This is a fixed-term appointment for 1 year.

Parkinson's disease affects more than ten million people worldwide, yet there is still no treatment that slows or prevents disease progression. Mutations that increase the activity of the kinase LRRK2 are among the most common genetic causes of the disease, and small-molecule LRRK2 inhibitors are now in clinical development. We are seeking an exceptional postdoctoral researcher to run and analyse the mass spectrometry experiments at the heart of this effort. Working at the interface of biochemistry, cell biology and quantitative proteomics, you will use state-of-the-art mass spectrometry to define how pathogenic LRRK2 mutations and LRRK2 inhibitors alter Rab GTPase phosphorylation and downstream lysosomal signalling, and to identify biomarkers of LRRK2 pathway activity in cell and patient-derived samples.

This is far more than a traditional postdoctoral position. The successful candidate will take ownership of the LRRK2 mass spectrometry workstream, with considerable freedom to develop new methods, pursue exciting biological questions and establish an international scientific profile.

The science and why it matters

LRRK2 is a large, multi-domain kinase, and gain-of-function mutations in LRRK2 are among the most common known genetic causes of Parkinson's disease. Once activated, LRRK2 phosphorylates a specific subset of Rab GTPases, including Rab10 and Rab12, disrupting the endolysosomal trafficking pathways these proteins control. Our goal is to define, with quantitative precision, how disease mutations and therapeutic LRRK2 inhibitors change this phosphorylation signalling in cells, animal models and patient-derived samples, and to turn these measurements into robust biomarkers of LRRK2 pathway activity.

This work sits within a wider, LITE-funded research programme, built around a major collaboration with Stanford University, that combines world-leading expertise in signal transduction, lysosome biology, clinical neurology and quantitative mass spectrometry to move seamlessly from mechanism to biomarker discovery and therapeutic opportunity.

This is a rare opportunity to help define how LRRK2 dysfunction drives Parkinson's disease while working with one of the world's most advanced proteomics platforms.

One of the world's most advanced proteomics platforms

You will have access to Orbitrap Astral, Orbitrap Exploris 480, Orbitrap Lumos and timsTOF SCP instruments anchored to Vanquish-Neo and EvoSep LC systems, supported by fully automated sample preparation using Agilent Bravo, Thermo KingFisher and cellenONE Neo-X1 platforms. Together these technologies enable ultra-sensitive quantitative proteomics from purified organelles, rare neuronal populations, patient-derived samples and single cells.

The team and environment

The MRC PPU is internationally recognised as one of the world's leading centres for signal transduction research. The programme brings together leading laboratories across the UK, Stanford University and the international LITE network, providing outstanding opportunities for collaboration, networking and career development.

What you'll do

• Run and analyse mass spectrometry experiments defining how LRRK2 mutations and inhibitors alter Rab GTPase phosphorylation and lysosomal signalling.
• Develop and apply next-generation organelle proteomics workflows, including Lyso-IP, to isolate LRRK2-relevant compartments.
• Generate deep quantitative proteomic, phosphoproteomic and ubiquitylomic datasets from cells, mouse models and patient-derived samples.
• Establish and validate mass spectrometry-based biomarkers of LRRK2 pathway activity for use in target engagement and clinical studies.
• Analyse large-scale datasets using Python, R and open-source computational tools.
• Publish discoveries in leading international journals.
• Mentor students and contribute to the scientific direction of the LRRK2 workstream.

What we offer

• One of the world's best-equipped academic proteomics environments.
• Ownership of the LRRK2 mass spectrometry workstream within a major international Parkinson's disease programme.
• Collaborations with Stanford University and the global LITE network.
• Advanced training in quantitative proteomics, computational biology and leadership.
• Support for independent research development.
• Relocation support for international applicants.
• Eligibility for LITE Care & Career Program family-care support.

Your priorities will include:

• Running and analysing mass spectrometry-based proteomics and post-translational modification (PTM) workflows relevant to LRRK2 signalling, including single cell proteomics.
• Applying organelle isolation workflows to generate high-resolution proteomics and PTM datasets.
• Using well established database search engines such as DIA-NN, MS-Fragger and Spectronaut, with subsequent data analysis in R/Python.
• Disseminating sample preparation protocols and data openly and through peer-reviewed publications.
• Participating in collaborative research and advising undergraduate and PhD students.

Who we're looking for:

You will have:

• A PhD (awarded or near completion) in a relevant discipline.
• A strong publication record, including first-author publication(s) appropriate to career stage.
• Expertise in two or more areas of:
  • Quantitative mass spectrometry and computational proteomics
  • Biochemistry and interest in signal transduction and/or translational research
  • Hands-on experience with Orbitrap and/or timsTOF instrumentation
  • Experience in analysing proteomics datasets using Python or R

Desirable

• Experience with biomarker studies or clinical samples.
• Interest in LRRK2 biology, neurodegeneration and translational science.

We are one of the UK's leading universities, internationally recognised for our expertise across a range of disciplines and research breakthroughs in multiple areas, including science, medicine and engineering, amongst many others. Our purpose is to transform lives, locally and globally, which we do as a community of staff (Professional Services and academic Faculties), students and alumni. Professional Services directorates are key to delivering the University strategy and driving change across the University.

For further information about this position please contact:

Dario Alessi d.r.alessi@dundee.ac.uk

Francesca Tonelli f.tonelli@dundee.ac.uk

To find out more about MRC PPU please visit https://www.ppu.mrc.ac.uk/

Commitment to DORA

The Faculty of Life Sciences has been fully committed to the principles of the San Francisco Declaration on Research Assessment (DORA) since 2013. In assessing applicants, we consider the scientific quality of their published research papers, but do not take into account where the papers were published and do not consider journal-based metrics, such as Journal Impact Factors.

As an internationally diverse institution, we welcome job applicants from all countries and nationalities. The Faculty of Life Sciences is proud to employ staff from over 40 different nations.

The diversity of our staff and students helps to make the University of Dundee a UK university of choice for undergraduate, postgraduate and distance learning. Family friendly policies, staff networks for BME, Disabled and LGBT staff, membership of Athena SWAN, the ECU Race Equality Charter and Stonewall as well a full range of disability services, create an enjoyable and inclusive place to work.