RNA Biology - Crispin Miller

Crispin studied Artificial Intelligence as an undergraduate before completing a PhD in Computational Biology, which focused on the development of fast pattern matching tools for Nucleotide and Protein Sequence analysis. He then followed his PhD with an MRC Training Fellowship in Bioinformatics. Crispin joined the CRUK Manchester Institute in 2002, and currently heads the RNA Biology Group.


The RNA Biology group is an interdisciplinary research group that combines High Performance Computing, Big Data analysis and computational research with molecular biology and clinical science.

We are focused on understanding how genetic changes to the noncoding genome lead to the development of lung and prostate cancer. We are particularly interested in the role played by long noncoding RNAs (lncRNAs) in regulating gene expression. lncRNAs are transcripts that are never translated into protein sequences. Deep sequencing studies, which have shown that as much as 80% of the genome is transcribed even though less than 2% directly encodes amino acids, have identified many thousands of lncRNAs. Overall, this work has revealed that there are more lncRNA genes in the genome than there are protein coding genes. Since they are a relatively recent discovery, only a handful have a known function. Our goal is to understand what they do in the cell, and what they do differently in cancer. To do this we are using next generation sequencing to find new lncRNAs that are expressed in human tumours, and are then comparing these results with cell line models, in which we are studying their function in detail.

Initially, much of this work was done in Schizosaccharomyces pombe, a type of yeast that expresses noncoding RNAs, and shares many of the important regulatory pathways with human cells. Our work not only identified new lncRNAs, but also allowed us to find additional protein coding genes. We are now applying what we have learnt from S. pombe to human cells.

The group also works closely with the Clinical and Experimental Pharmacology (CEP) group, asking how circulating tumour cells (CTCs) can help us understand cancer, and we are members both of the CRUK Lung Cancer Centre of Excellence and the MRC Single Cell Research Centre. We make use of the Institute’s large (2,000 core) HPC system, and researchers in the group include computer scientists, mathematicians as well as biologists and clinicians.

Selected Publications


Hudson AM, Stephenson NL, Li C, Trotter E, Fletcher AJ, Katona G, Bieniasz-Krzywiec P, Howell M, Wirth C, Furney S, Miller CJ, Brognard J. (2018)
Truncation- and motif-based pan-cancer analysis reveals tumor-suppressing kinases.
Science Signaling 11(526) pii: eaan6776. PubMed abstract

Carter L, Rothwell D, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F, Li Y, Burt D, Antonello J, Morrow C, Hodgkinson C, Morris K, Priest L, Carter M, Miller C, Hughes A, Blackhall F, Dive C, Brady G. (2017)
Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer.
Nature Medicine 23(1):114-119. PubMed abstract

Memon D, Dawson K, Smowton CSF, Xing W, Dive C, Miller CJ. (2016)
Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response.
npj Genomic Medicine 1:16020. Article

Hudson AM, Wirth C, Stephenson NL, Fawdar S, Brognard J, Miller CJ. (2015)
Using large-scale genomics data to identify driver mutations in lung cancer: Methods and challenges.
Pharmacogenomics 16 (10):1149-1160. PubMed abstract

Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F, Polanski R, Burt DJ, Simpson KL, Morris K, Pepper S, Nonaka D, Greystoke A, Kelly P, Bola B, Krebs MG, Antonello J, Ayub M, Faulkner S, Priest L, Carter L, Tate C, Miller CJ, Blackhall F, Brady G & Dive C. (2014)
Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. 
Nature Medicine 20(8):897-903.  PubMed abstract

Leong HS, Dawson K, Wirth C, Li Y, Connolly Y, Smith DL, Wilkinson CRM, Miller CJ. (2014)
A global non-coding RNA system modulates fission yeast protein levels in response to stress.
Nature Communications 5:3947. PubMed abstract

Bitton DA, Wood V, Scutt PJ, Grallert A, Yates T, Smith DL, Hagan IM, Miller CJ. (2011)
Augmented annotation of the Schizosaccharomyces pombe genome reveals additional genes required for growth and viability.
Genetics, 187 (4):1207-1217. PubMed abstract

Bitton DA, Grallert A, Scutt PJ, Yates T, Li Y, Bradford JR, Hey Y, Pepper SD, Hagan IM, Miller CJ. (2011)
Programmed fluctuations in sense/antisense transcript ratios drive sexual differentiation in S. pombe
Molecular Systems Biology, 7 (1):559. PubMed abstract

Buffa FM, Harris AL, West CM, Miller CJ. (2010)
Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene.
British Journal of Cancer 102 (2): 428-435. PubMed abstract

Bitton DA, Smith DL, Connolly Y, Scutt PJ, Miller CJ. (2010)
An integrated mass-spectrometry pipeline identifies novel protein coding-regions in the human genome.
PLoS ONE 5 (1):e8949. PubMed abstract

Yates T, Okoniewski MJ, Miller CJ. (2008)
X:Map: Annotation and visualization of genome structure for Affymetrix exon array analysis.
Nucleic Acids Research 36(Database issue):D780-6.PubMed abstract



Scientific Officer
Keren Dawson

Postdoctoral Fellows
Laura Bennet
Jing Bi
Garima Khandelwal
Chang Kim

Graduate Students
Sam Humphrey
Mairah Khan
Ronnie Rodrigues Pereira

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