Liina Sirvio

Project Title: Alpha-synuclein aggregates are targeted for degradation by phase-separated proteasome droplets
Supervisor: Dr Yu Ye, Professor Steve Gentleman
Location: Level 7, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, W12 0BZ

About Me

I am a PhD student in the Department of Brain Sciences at Imperial College London, investigating the role of post-translational modifications of amyloid proteins in the pathogenesis of Alzheimer’s and Parkinson’s diseases. Prior to starting my PhD, I completed my BSc in Biochemistry at King's College London, MRes at Imperial, and worked as a research technician in the Kinases and Brain Development laboratory at The Francis Crick Institute.

Qualifications

2018-2019: MRes Molecular and Cellular Biosciences, Imperial College London
2015-2018: BSc Biochemistry, King’s College London

Research Interests

Post-translational modifications on amyloid proteins have been shown to have critical roles involved in their aggregation behaviour. Enhanced phosphorylation and ubiquitination have been found in tau tangles in Alzheimer’s disease (AD) and Lewy Bodies in Parkinson’s disease (PD). In addition, both ubiquitinating and deubiquitinating enzymes, as well as ubiquitin-dependent degradation through the proteasome, have been implicated in AD and PD. Understanding the key enzymatic activities that drive toxic protein aggregation is therefore critical to identify novel targets of therapeutic intervention to slow and reverse neurodegeneration.

The aim of my PhD project is to study how alpha-synuclein aggregates are targeted by proteasomes for degradation and why aggregates are not cleared in neurodegenerative diseases. My project combines biochemistry and cell biology approaches with advanced super-resolution microscopy techniques.

Publications

Morten M., Sirvio L., Rupawala H., Mee Hayes E., Franco Budia A., Radulescu C., Rupawala H., Ying L., Barnes SJ., Muga A., Ye Y. “Quantitative super-resolution imaging of pathological aggregates reveals distinct toxicity profiles in different synucleinopathies.” Proceedings of the National Academy of Sciences, vol. 119, no. 41, 2022, https://doi.org/10.1073/pnas.2205591119

Mee Hayes E., Sirvio L., Ye Y. “A potential mechanism for targeting aggregates with proteasomes and disaggregases in liquid droplets.” Frontiers in Aging Neuroscience, vol. 14, 2022, https://doi.org/10.3389/fnagi.2022.854380

Presentations and conferences attended

"Aggregates are Targeted for Degradation by Phase-Separated Proteasome Droplets" at the Stress Proteins in Growth, Development and Disease Gordon Research Seminar (GRS) - July 1-2, 2023
Stress Proteins in Growth, Development and Disease Gordon Research Conference - July 2-7, 2023

Professional memberships

Biochemical Society

Contact Details

Email: les18@imperial.ac.uk
LinkedIn: liina-sirvio

How temperature and circadian rhythms intersect to regulate a protein shown to protect against neurodegeneration

A new study led by Dr Marco Brancaccio (UK DRI at Imperial) and Dr Marieke Hoekstra (former UK DRI at Imperial, now VIB-KU Leuven Center for Brain & Disease Research) offers a deeper insight into how a neuroprotective pathway is regulated both by temperature and the body clock. This research, published in the journal PNAS, could open up new therapeutic avenues for neurodegenerative disease.
Read more on the UK DRI website

Introducing Cynthia Sandor: Pioneering earlier detection of Parkinson’s

Dr Cynthia Sandor, former Emerging Leader at the UK DRI at Cardiff, joins the UK DRI at Imperial as a Group Leader, where she will be tackling early diagnosis of Parkinson’s.

With a background in genetics, Dr Sandor uses computational methods to bring greater understanding to the underlying molecular mechanisms of Parkinson’s. Read more about Cynthia's work on the UK DRI website.

Ageing brain fails to control neuronal activity with consequences for cognition

Age-linked cognitive decline findings from our UK DRI Centre

Ageing brain fails to control neuronal activity with consequences for cognition, according to a study led by Dr Sam Barnes and Dr Carola Radulescu. Read more on the UK DRI website.

Ancient DNA reveals reason for high MS and Alzheimer’s rates in Europe

Groundbreaking study of ancient genes provides brand new biological understanding of debilitating disorders

Researchers have created the world’s largest ancient human gene bank by analysing the bones and teeth of almost 5,000 humans who lived across western Europe and Asia up to 34,000 years ago. By sequencing ancient human DNA and comparing it to modern-day samples, the international team of experts mapped the historical spread of genes – and diseases – over time as populations migrated.

Read more on the University of Cambridge website.

Health Minister visits White City to see pioneering dementia research

The Minister for Health and Secondary Care Andrew Stephenson MP visited the UK Dementia Research Institute at White City.

The new Minister for Health and Secondary Care Andrew Stephenson MP visited Imperial's White City Campus yesterday to see the work of the UK Dementia Research Institute Care Research and Technology Centre based at the Sir Michael Uren Hub. The Minister was hosted by Professor Deborah Ashby, Interim Dean of the Faculty of Medicine, and Professor Siddharthan Chandran, Director of the UK Dementia Research Institute. Read more on the Imperial news website.

New non-invasive form of deep brain stimulation could provide alternative treatment for brain diseases

Cutting-edge work led by Imperial PI Dr Nir Grossman makes national press

Scientists from the UK Dementia Research Institute centre at Imperial College London featured on ITV News and in national newspapers. Read more on the Imperial website and the UK DRI website.

Imperial named UK’s best university

Imperial College London is ranked top of a new league table of UK universities.

Imperial has also been named University of the Year in the league table, published by the Daily Mail, and is praised for its "sustained excellence in all areas” alongside its commitment to social inclusion, including generous bursary support.

Read full article.

The UK Dementia Research Institute is a joint £290 million investment from the Medical Research Council (MRC), Alzheimer’s Society and Alzheimer’s Research UK.