Reader, University of Aberdeen
1999 - 2003
Senior Lecturer, University of Aberdeen
Group Leader, Institute for Cell Biology, Bern University (Switzerland)
Post-doctoral Research Fellow and Visiting Scientist, Clare Hall Laboratories, Imperial Cancer Research Fund (now Cancer Research UK)
PhD, Swiss Federal Institute of Technology in Zürich
Diploma in Natural Sciences, Swiss Federal Institute of Technology in Zürich
The lab has a long-standing interest in the control of gene expression at the level of mRNA. This started in 1993, when Berndt joined the University of Bern where he worked with Prof Daniel Schümperli. Prior to that he did his PhD in the group of Prof Theo Koller at the Institute of Cell Biology of the ETH in Zürich, with Dr Andrzej Stasiak and Dr Elisabeth DiCapua, analysing the interaction of the recombination protein RecA protein with DNA. He then spent 5 years in the lab of Dr Steve West at Cancer Research UK studying the Biochemistry of Genetic Recombination. At Bern University, he identified factors that control the processing of histone RNA to mature mRNA. This work was continued at the University of Aberdeen and has led to insight into the molecular function of these factors.
More recently our research focuses on two other aspects of RNA metabolism: the mechanism of spliced leader trans-splicing in gene expression in nematodes, and the role of post-transcriptional control of gene expression in neuronal differentiation.
With colleagues Jonathan Pettitt and Bernadette Connolly we are investigating the role of spliced leader trans-splicing in nematodes. Spliced leader trans-splicing results in the addition of a short capped mRNA sequence to the 5’ end of mRNAs by a process related to mRNA cis-splicing, the process resulting in the removal of introns. We have shown that this essential process is conserved and occurs in nematodes very distantly related to the model organism C. elegans (Pettitt et al 2008; Harrison et al 2010). Spliced leader trans-splicing is required for the processing of operon transcripts prior to translation. We are interested in understanding the fundamentals of this process and how this understanding can be applied to fight nematode plant and animal pathogens. We have created an in vivo assay to monitor trans-splicing in living C. elegans, and have found that the SL trans-splicing requires SMN protein linked to spinal muscular atrophy in humans splicing and is highly sensitive to a reduction of the levels of a group of RNA binding proteins also involved in “normal” splicing (Philippe et al 2017).
Spliced leader trans-splicing is linked to the presence of operons in eukaryotes, a feature of genome organisation conserved across the nematode phylum (Pettitt et al 2014). We have recently reported that in nematodes, the spliced leader RNAs that act on operon transcripts to create capped, monocistronic transcripts that can be translated, share sequence elements critical for function (https://www.biorxiv.org/content/10.1101/642082v1). This provides important new insight into the evolution of this process.
We have previously linked the key translation factor eIF4E to autism (Neves-Pereira et al 2009). To understand how deregulation of eIF4E contributes to the development of autism causes we are currently examining the effects of eIF4E overexpression on neuronal differentiation.
Biochemistry Programme Co-ordinator
Course co-ordination of BC3503 (The Molecular Control of Cell Function) and BC4314 (Honours Biochemistry Option 2).
Teaching in MB3006, SM3001, BC3503, MB4050 and BC4314.
- Further Info
Current Lab Members
Ammar Alturkistani, Svetlozara Chobanova, Rotimi Fasimoye, Rosie Spencer, Andrew Strange
Page 1 of 5 Results 1 to 10 of 46
- Khatib, T, Whiting, A, Chisholm, DR, Redfern, C, Muller, B & McCaffery, P 2019, 'A Bioluminescence Reporter Assay for Retinoic Acid Control of Translation of the GluR1 Subunit of the AMPA Glutamate Receptor', Molecular Neurobiology, vol. 56, no. 10, pp. 7074-7084. [Online] DOI: https://doi.org/10.1007/s12035-019-1571-9
- Pandarakalam, GC, Speake, M, McElroy, S, Alturkistani, A, Philippe, L, Pettitt, J, Muller, B & Connolly, B 2019, 'A high-throughput screen for the identification of compounds that inhibit nematode gene expression by targeting spliced leader trans-splicing', International Journal for Parasitology: Drugs and Drug Resistance, vol. 10, pp. 28-37. [Online] DOI: https://doi.org/10.1016/j.ijpddr.2019.04.001
- Philippe, L, Pandarakalam, GC, Fasimoye, R, Harrison, N, Connolly, B, Pettitt, J & Muller, B 2017, 'An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly', Nucleic Acids Research, vol. 45, no. 14, pp. 8474-8483. [Online] DOI: https://doi.org/10.1093/nar/gkx500
- Christopher, A, Hameister, H, Corrigall, H, Ebenhoeh, O, Muller, B & Ullner, E 2016, 'Modelling Robust Feedback Control Mechanisms That Ensure Reliable Coordination of Histone Gene Expression with DNA Replication', PloS ONE, vol. 11, no. 10, e0165848. [Online] DOI: https://doi.org/10.1371/journal.pone.0165848
- Alrahbeni, T, Sartor, F, Anderson, J, Miedzybrodzka, Z, McCaig, C & Muller, B 2015, 'Full UPF3B function is critical for neuronal differentiation of neural stem cells', Molecular brain, vol. 8, 33. [Online] DOI: https://doi.org/10.1186/s13041-015-0122-1
- Sartor, F, Anderson, J, McCaig, C, Miedzybrodzka, Z & Müller, B 2015, 'Mutation of genes controlling mRNA metabolism and protein synthesis predisposes to neurodevelopmental disorders', Biochemical Society Transactions, vol. 43, no. 6, pp. 1259-1265. [Online] DOI: https://doi.org/10.1042/BST20150168
- Pettitt, J, Philippe, L, Sarkar, D, Johnston, C, Gothe, H, Massie, D, Connolly, B & Muller, B 2014, 'Operons Are a Conserved Feature of Nematode Genomes', Genetics, vol. 197, no. 4, pp. 1201-1211. [Online] DOI: https://doi.org/10.1534/genetics.114.162875
- Rattray, AMJ, Nicholson, P & Muller, B 2013, 'Replication stress-induced alternative mRNA splicing alters properties of the histone RNA-binding protein HBP/SLBP: a key factor in the control of histone gene expression', Bioscience Reports, vol. 33, no. 5, e00066. [Online] DOI: https://doi.org/10.1042/BSR20130074
- Rattray, AM & Muller, BM 2012, 'The control of histone gene expression', Biochemical Society Transactions, vol. 40, no. 4, pp. 880-885. [Online] DOI: https://doi.org/10.1042/BST20120065
- Harrison, N, Kalbfleisch, A, Connolly, B, Pettitt, J & Muller, B 2010, 'SL2-like spliced leader RNAs in the basal nematode Prionchulus punctatus: new insight into the evolution of nematode SL2 RNAs', RNA , vol. 16, no. 8, pp. 1500-1507. [Online] DOI: https://doi.org/10.1261/rna.2155010