Nucleic Acids and Innate Immunity Research Group
Research Group Head
Lab focus: nucleic acids in immune responses
Most people will know about DNA, and perhaps a little about RNA. DNA and RNA constitute a class of molecules referred to as nucleic acids, which are essential to all forms of life known to date. They contain and access the genetic information that controls which cells do what in our bodies. Critically, because they are present in every form of life including bacteria and viruses, they are also essential for our immune system to detect infections.
Our laboratory is interested in defining how nucleic acids control the interface between host and pathogens, and how this can lead to inflammatory diseases (as seen in Systemic Lupus Erythematosus).
With several new nucleic acids-based therapies now approved for use in humans (to treat diseases such as spinal muscular atrophy), understanding how synthetic nucleic acids can influence normal immune responses is important. In addition, synthetic nucleic acids can be devised to curb infections, presenting high potential against emerging global threats. Many chemotherapies directly interact with nucleic acids, indirectly engaging our immune system. Finally, nucleic acids circulating in the blood present many advantages for disease detection and prognosis.
Our group has made significant findings relevant to these themes – for instance recently describing how acriflavine, a century old antiseptic that binds DNA, can also induce immune responses protective against viruses.
Current research projects
- In line with our findings on acriflavine, we are now working to understand how chemotherapies recruit the immune system (through activation of the sensor known as cGAS) – with potential direct involvements in cancer treatment. We are also looking at how these compounds could be repurposed as broad antiviral and antibacterial agents.
- Relying on more than 10 years’ expertise in synthetic nucleic acids, we are studying how such synthetic molecules could be designed to prevent auto-immunity and fight bacterial infections.
- Finally, we are also studying the role of microRNAs in the regulation of infection and immunity. We have a specific focus on mechanisms regulating microRNA stability, and how this knowledge can be used to create novel biomarkers of autoinflammation and cancer (for instance defining novel pathogenic BRCA1 mutations).
If you are looking for a great workplace to carry out an honours, PhD or Masters project, please contact us to see how the nucleic acids and therapeutics lab could help you make a lasting impact in your next scientific endeavour.
Pepin G, Nejad C, Thomas BJ, Ferrand J, McArthur K, Bardin PG, Williams BR, Gantier MP (2017) Activation of cGAS-dependent antiviral responses by DNA intercalating agents. Nucleic Acids Res 45:198-205.
Pepin G, Ferrand J, Honing K, Jayasekara WS, Cain JE, Behlke MA, Gough DJ, Williams BRG, Hornung V, Gantier MP (2016) Cre-dependent DNA recombination activates a STING-dependent innate immune response. Nucleic Acids Res 44:5356-5364.
Sarvestani ST, Stunden HJ, Behlke MA, Forster SC, McCoy CE, Tate MD, Ferrand J, Lennox KA, Latz E, Williams BRG, Gantier MP (2015) Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors. Nucleic Acids Res 43(2):1177-1188.
Sarvestani ST, Tate MD, Moffat JM, Jacobi AM, Behlke MA, Miller AR, Beckham SA, McCoy CE, Chen W, Mintern JD, O’Keeffe M, John M, Williams BRG, Gantier MP (2014) Inosine-Mediated Modulation of RNA Sensing by TLR7/8. J Virol 88(2):799-810.
Wu D, Hu Y, Tong S, Williams BR, Smyth GK, Gantier MP (2013) The use of miRNA microarrays for the analysis of cancer samples with global miRNA decrease. RNA 19:876-88.
Gantier MP, Stunden HJ, McCoy CE, Behlke MA, Wang D, Kaparakis-Liaskos M, Sarvestani ST, Yang YH, Xu D, Corr SC, Morand EF, Williams BR (2012) A miR-19 regulon that controls NF-kappaB signaling. Nucleic Acids Res 40:8048-58.
Gantier MP, McCoy CE, Rusinova I, Saulep D, Wang D, Xu D, Irving AT, Behlke MA, Hertzog PJ, Mackay F, Williams BR (2011) Analysis of microRNA turnover in mammalian cells following Dicer1 ablation. Nucleic Acids Res 39:5692-703.
Gantier MP, Tong S, Behlke MA, Irving AT, Lappas M, Nilsson UW, Latz E, McMillan NA, Williams BR (2010) Rational design of immunostimulatory siRNAs. Mol Ther 18:785-95.
Gantier MP, Irving AT, Kaparakis-Liaskos M, Xu D, Evans WA, Cameron PU, Bourne JA, Ferrero RL, John M, Behlke MA, Williams BR (2010) Genetic modulation of TLR8 response following bacterial phagocytosis. Human Mutation 31:1069-79.
Gantier MP, Tong S, Behlke MA, Xu D, Phipps S, Foster PS, Williams BR (2008) TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages. J Immunol 180:2117-24.
Pépin G, Nejad C, Ferrand J, Thomas BJ, Stunden HJ, Sanij E, Foo CH, Stewart CR, Cain JE, Bardin PG, Williams BRG, Gantier MP (2017) Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses. MBio 8(5):e01611-17
Nejad C, Pillman KA, Siddle KJ, Pepin G, Änkö ML, McCoy CE, Beilharz T, Quintana-Murci L, Goodall GJ, Bracken CP, Gantier MP (2017) miR-222 isoforms are differentially regulated by type-I interferon. RNA pii: rna.064550.117. doi: 10.1261/rna.064550.117.