Raja Nirujogi opens Independent Investigator laboratory within the MRC PPU

Raja has a joint appointment between the Universities of Dundee and Edinburgh and will spend significant time working in both institutions.

Raja has made a major contribution to the research on the LRRK2 pathway and development of mass spectrometry in the MRC-PPU. He developed widely used quantitative mass spectrometry (MS) assays to assess levels of LRRK2 phosphorylated Rab proteins in cells and tissues as well as clinical samples. Raja also contributed greatly to the establishment of robust methods and detailed protocols for the TMT and DIA workflows that are widely used throughout the PPU and his technology developments and research were crucial for other work that led to the identification of novel substrates of SGK3, NUKA1 and NUAK2. More recently working with Toan Phung, Raja also made a major input into development of the data visualisation CURTAIN tool that enables non experts to peruse MS data that is becoming widely used in the Unit and beyond. Raja has also collaborated and provided significant support to many external groups over this period including those working at the University of Edinburgh Anne Rowling Regenerative Neurology Clinic, UK Dementia Research Institute and Aligning Science Across Parkinson’s network.

As an Independent Investigator, Raja’s research programme is centred on deciphering signalling pathways in amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), focusing initially on TDP-43 and C9orf72 proteins to define how mutations in these proteins impact motor neurons. Much evidence suggests that mutations in TDP-43 and likely other ALS genes impact splicing leading to expression of cryptic exons. Raja will work closely with the UK Dementia Research Institute at the University of Edinburgh and Euan MacDonald Centre for MND Research researchers who have developed state of the art induced pluripotent stem cell models of ALS. Raja will exploit these models to develop quantitative MS assays to better understand how mutations impact motor neuron cell biology and function. In parallel, and in partnership, with researchers at the Euan MacDonald Centre and linked Anne Rowling Regenerative Neurology Clinic, Raja will also develop new methods to detect ALS-specific cryptic peptides encoded by these spliced proteins and to assess whether these assays can be used diagnostically to monitor ALS disease subtype and/or disease progression. Raja, working with UK DRI based researchers, also intends over time to establish and exploit ultrasensitive single cell and spatial proteomics methodologies as both a discovery and clinical translational resource with a focus on ALS and related conditions such as fronto-temporal dementias.

Raja said “I am very excited and feel privileged to be an Independent Investigator within MRC-PPU. I am delighted to be able to apply many of the skills I have learnt over the years to help improve our understanding of MND and related neurodegenerative conditions. I am particularly pleased to be able to work across the MRC PPU and UK DRI with the enormous added value of collaborating with leading clinicians and scientists at Edinburgh. I very much hope that my research programme, for which I will seek fellowship grant support, will open new avenues in understanding disease mechanism as well as lead to the development of new biomarkers for MND. I am very grateful to Dario Alessi and Siddharthan Chandran (UK-DRI Edinburgh) for their support".