Dr Julie Aspden

Profile

My group addresses questions on the regulation of mRNA translation, non-coding RNA function and the role of specific RNA-protein complexes. I combine biochemistry, genomics, molecular biology and genetics to study RNAs in fruit flies and mammalian tissue culture. Drosophila is an idea model for this work because it is amenable to genetic characterisations, suitable for biochemical purifications of material from organisms and tissue culture cells and the quality of genomic data available is excellent. Many of the regulatory processes and RNA-binding proteins are highly conserved between Drosophila and mammals.

I read Biochemistry at The Queen’s College, Oxford before undertaking a PhD in Biochemistry at the University of Cambridge on the initiation of mRNA translation. During my first postdoc at the University of California, Berkeley, my work focused on alternative mRNA splicing in the fruit fly. My second postdoc was at the University of Sussex, where I defined novel regions of translation. In 2015 I was awarded a University Academic Fellowship in Pervasive Transcription reflected by my interest in the function and biological impact of RNAs. This fellowship allowed me to establish my own research group here at Leeds in August 2015.

Responsibilities

• PI for "Ribo-Code" BBSRC sLoLa
• Academic lead of LeedsOmics

Research interests

Regulation of mRNA translation

Canonical initiation involves the recruitment of the 40S ribosome to the 5' end of the mRNA. The 40S then scans through the 5'-UTR to find the start codon, where the 60S joins and elongation begins. We are interested in how translation is regulated during initiation, especially by the 5'-UTR and associated proteins. Disruptions to RNA-protein interactions and translational regulation play significant roles in a variety of cancers and other disorders (e.g. spinal muscular atrophy).

Long non-coding RNAs in the cytoplasm

Whilst the majority of our genome is transcribed, only a small fraction is protein-coding. This implies that many non-coding RNAs exist, some of which are similarly processed to mRNAs, termed long non-coding RNAs (lncRNAs). The majority of characterised lncRNAs are nuclear but recent ribosome profiling results have revealed that many are translated. Although controversial, it is clear that numerous lncRNAs are cytoplasmic, polysome-associated and translated. The line between coding and non-coding has become blurred and some lncRNAs are really mRNAs. LncRNAs are enriched in neuronal tissues and several have been found associated with neurological conditions e.g. Alzheimer’s disease. To better understand the molecular basis of neuronal disease it is vital that we appreciate the role of cytoplasmic lncRNAs in regulating gene expression. We are studying the function of these cytoplasmic lncRNAs.

mRNP history

mRNAs are at the centre of gene expression, providing translational machinery with a copy of the genetic code. Proteins interact with sequence elements within mRNAs to ensure accurate mRNA processing. The identity of proteins bound to mRNAs changes as they participate in different events. RNA-binding proteins interact with RNAs as soon as they are transcribed in the nucleus. Some of these interactions regulate nuclear RNA processing events such as splicing. Other RNA-binding proteins affect the translation of mRNAs as well eg. PTB. The extent to which these nuclear associations continue as mRNAs are exported from the nucleus to the cytoplasm is not yet clear. The changing composition of these complexes is likely to be highly regulated and affect to what extent mRNAs are translated into proteins. Our long-term goal is to understand how RNA processing in the nucleus affects translation in the cytoplasm and how disturbing mRNP composition can be detrimental to the cell.

Research is currently funded by: 

• MRC
• BBSRC
• Royal Society

• How does Chikungunya virus regulate the switch between genome translation and replication?
• How does Chikungunya virus regulate the switch between genome translation and replication?
• The epigenetic control temperature-induced flowering

Qualifications

• M. Biochem, University of Oxford (The Queen's College)
• PhD in Biochemistry, University of Cambridge (Selwyn College)
• Postdoctoral work with Professor Don Rio, University California, Berkeley, USA (2006 - 2011)
• Post-doctoral work with Professor Juan Pablo Couso, University of Sussex, UK (2012 - 2015)

Professional memberships

• RNA Society
• Biochemistry Society
• Genetics Society

Student education

Postgraduate studentship areas:

• Faculty Graduate School

Research groups and institutes

• Heredity, Development and Disease
• Cancer
• Cell and Organismal Biology

Current postgraduate researchers

• James Murphy
• Mr Ioannis Tsagakis