The Node’s primary research interest is investigating the regulation of the innate immune system from a genome-wide or systems level perspective. The innate immune system is subsystem of the overall immune system. It is responsible for defending the host from infection and is primarily found in plants, insects, fungi and other, evolutionarily older, multicellar organisms. 

Research
In their research, the Lynn Node uses in vitro and in vivo (mouse) experimental models coupled with systems biology approaches to investigate the regulation of innate immunity.

One of the recent focuses of the node is the relationship between the immune system and the microbiome. Additionally, the Lynn group are looking at what effect vaccines on mortality and morbidity outside of preventing the targeted diseases, as well as seeing how particular vaccines can assist immune cells to be more responsive to unrelated antigens.

David has developed a node that applies similar integrative biology approaches as described above to human health and he has a particular interest in the role of microRNAs in regulating innate immunity networks. David's node will also continue to develop novel computational analysis tools to facilitate this research including new network analysis and visualization tools. David will also continue to lead the development of InnateDB (http://www.innatedb.com/), a computational analysis platform for studying innate immune networks, which is used worldwide by thousands of users.

David has also expanded his interest in network biology into the cancer signaling area, and he leads the computational biology aspects of €12 million European Commission funded project called PRIMES, which is investigating how to model and subsequently therapeutically target protein interaction networks in cancer. 

  • Regulatory mechanisms of the human innate immune system
  • Investigating how dysregulation of the neonatal gut microbiome (mouse and human) affects subsequent immune responses (for example, to childhood immunisations)
  • The development of InnateDB.com, an internationally recognised systems biology platform for the computational analysis of innate immunity networks/pathways
  • Biology aspects of the PRIMES project, a 13-partnerproject (approximately €12 million funded by the European Commission) that is investigating network rewiring in colorectal cancer​

​​Systems Immunology

  • The impact of the microbiota in early-life on the developing immune system and optimal vaccine responses.
  • How does the microbiota modulate vaccine responses in human infants: A systems vaccinology approach.
  • Vaccine non-specific effects and trained innate immunity.
  • The impact of the microbiota on the efficacy and toxicity of cancer immunotherapies.
  • InnateDB an internationally recognised platform facilitating systems level analyses of innate immunity.
  • Gnotobiotic (germ-free) mouse models.

Bioinformatics and Computational Biology

  • The development of novel software applications and resources for proteomics, pathway analysis, network analysis and visualisation (e.g. DyNet; CHAT; SIGORA; HiQuant).
  • Protein-Protein Interaction Network Rewiring in Cancer (International PRIMES consortium).
  • Patient-Specific Network Rewiring.
  • Transcriptional and metabolic reprogramming of colorectal cancer cells expressing the oncogenic KRASG13D mutation.
  • Novel co-extinction strategies for treatment of prostate cancer.
  • Network visualization and analysis of spatial omics data.
Authors
Title
Published In

Muetze T, Goenawan IH, Wiencko HL, Bernal-Llinares M, Bryan K, Lynn DJ. 

Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks.

F1000 Research 2016 (In press).

Goenawan IH, Bryan K, Lynn DJ. (Corresponding Author)

DyNet: visualization and analysis of dynamic molecular interaction networks.

Bioinformatics. 2016 Sep 1;32(17):2713-5. doi: 10.1093/bioinformatics/btw187. Epub 2016 May 3.

Bryan K, Jarboui MA, Raso C, Bernal-Llinares M, McCann B, Rauch J, Boldt K, Lynn DJ. (Corresponding Author)

HiQuant: Rapid Postquantification Analysis of Large-Scale MS-Generated Proteomics Data.

J Proteome Res. 2016 Jun 3;15(6):2072-9. doi: 10.1021/acs.jproteome.5b01008. Epub 2016 May 16.

Blohmke CJ, Darton TC, Jones C, Suarez NM, Waddington CS, Angus B, Zhou L, Hill J, Clare S, Kane L, Mukhopadhyay S, Schreiber F,Duque-Correa MA, Wright JC, Roumeliotis TI, Yu L, Choudhary JS, Mejias A, Ramilo O, Shanyinde M, Sztein MB, Kingsley RA, Lockhart S,Levine MM, Lynn DJ, Dougan G, Pollard AJ.

Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.

J Exp Med. 2016 May 30;213(6):1061-77. doi: 10.1084/jem.20151025. Epub 2016 May 23.

Charitou T, Bryan K, Lynn DJ. (Corresponding Author)

Using biological networks to integrate, visualize and analyze genomics data.

Genet Sel Evol. 2016 Mar 31;48:27. doi: 10.1186/s12711-016-0205-1.

Richardson IW, Berry DP, Wiencko HL, Higgins IM, More SJ, McClure J, Lynn DJ, Bradley DG.

A genome-wide association study for genetic susceptibility to Mycobacterium bovis infection in dairy cattle identifies a susceptibility QTL on chromosome 23.

Genet Sel Evol. 2016 Mar 9;48:19. doi: 10.1186/s12711-016-0197-x.

Foley C, Chapwanya A, Callanan JJ, Whiston R, Miranda-CasoLuengo R, Lu J, Meijer WG, Lynn DJ, O' Farrelly C, Meade KG.

Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis.

BMC Genomics. 2015 Oct 19;16:811. doi: 10.1186/s12864-015-1967-5.

Frias S, Bryan K, Brinkman FS, Lynn DJ. (Corresponding Author)
 
 

CerebralWeb: a Cytoscape.js plug-in to visualize networks stratified by subcellular localization.

Database (Oxford). 2015 May 7;2015:bav041. doi: 10.1093/database/bav041. Print 2015.

Vegh P, Foroushani ABK, Magee DA, McCabe MS, Browne JA, Nalpas NC, Conlon KM, Gordon SV, Bradley DG, MacHugh DE, Lynn DJ (Corresponding Author).

Profiling microRNA expression in bovine alveolar macrophages using a next-generation sequencing based approach.

Tuberculosis (Edinb). 2015 Jan;95(1):60-7.

Dickinson P, Smith CL, Forster T, Craigon M, Ross AJ, Khondoker MR, Ivens A, Lynn DJ, Orme J, Jackson A, Lacaze P, Flanagan KL, Stenson BJ, Ghazal P.

Whole blood gene expression profiling of neonates with confirmed bacterial sepsis.

Genom Data. 2014 Nov 15;3:41-8. doi: 10.1016/j.gdata.2014.11.003. eCollection 2015.

Fatima A, Lynn DJ (Corresponding Author), O’Boyle P, Seoighe C, Morris D.

The miRNAome of the postpartum dairy cow liver under negative energy balance.

BMC Genomics. 2014 Apr 12;15:279. doi: 10.1186/1471-2164-15-279.

Lawless N, Reinhardt TA, Bryan K, Baker M, Pesch B, Zimmerman D, Zuelke K, Sonstegard T, O’Farrelly C, Lippolis JD, Lynn DJ (Corresponding Author).

MicroRNA regulation of bovine monocyte inflammatory and metabolic networks in an in vivo infection model.

G3 (Bethesda). 2014 Jan 27;4(6):957-71. doi: 10.1534/g3.113.009936.

Foroushani A, Brinkman FSL, Lynn DJ (Corresponding Author).

Pathway-GPS and SIGORA: Identifying relevant pathways based on the over-representation of their gene-pair signatures.

PeerJ. 2013 Dec 19;1:e229. doi: 10.7717/peerj.229. eCollection 2013.

Meredith BK, Berry DP, Kearney JF, Finlay EK, Fahey AG, Bradley DG, Lynn DJ (Corresponding Author).

A Genome-wide association study for somatic cell score using the illumina high-density bovine BeadChip identifies several novel QTL potentially related to mastitis susceptibility.

Front Genet. 2013 Nov 6;4:229. doi: 10.3389/fgene.2013.00229. eCollection 2013.

Lawless N, Foroushani AK, McCabe M, O’Farrelly C, Lynn DJ (Corresponding Author).

Next generation sequencing reveals the expression of a unique miRNA profile in response to a Gram-positive bacterial infection.

PLoS One. 2013;8(3):e57543. doi: 10.1371/journal.pone.0057543. Epub 2013 Mar 5.

Achtman AH, Pilat S, Law CW, Lynn DJ, Janot L, Mayer ML, Ma S, Kindrachuk J, Finlay BB, Brinkman FSL, Smyth GK, Hancock REW, Schofield L.

Effective adjunctive therapy by an innate defense regulatory Peptide in a preclinical model of severe malaria.

Sci Transl Med. 2012 May 23;4(135):135ra64. doi: 10.1126/scitranslmed.3003515.

Orchard S, Kerrien S, Abbani S, Aranda B, Bhate J, Bidwell S, Bridge A, Briganti L, Brinkman FS, Cesareni G, Chatr-aryamontri A, Chautard E, Chen C, Dumousseau M, Goll J, Hancock RE, Hannick LI, Jurisica I, Khadake J, Lynn DJ, Mahadevan U, Perfetto L, Raghunath A, Ricard-Blum S, Roechert B, Salwinski L, Stümpflen V, Tyers M, Uetz P, Xenarios I, Hermjakob H.

Protein Interaction Data Curation - The International Molecular Exchange Consortium (IMEx).

Nat Methods. 2012 Apr;9(4):345-50. doi: 10.1038/nmeth.1931.

Aranda B, Blankenburg H, Kerrien S, Brinkman FS, Ceol A, Chautard E, Dana JM, De Las Rivas J, Dumousseau M, Galeota E, Gaulton A, Goll J, Hancock RE, Isserlin R, Jimenez RC, Kerssemakers J, Khadake J, Lynn DJ, Michaut M, O'Kelly G, Ono K, Orchard S, Prieto C, Razick S, Rigina O, Salwinski L, Simonovic M, Velankar S, Winter A, Wu G, Bader GD, Cesareni G, Donaldson IM, Eisenberg D, Kleywegt GJ, Overington J, Ricard-Blum S, Tyers M, Albrecht M, Hermjakob H.

PSICQUIC and PSISCORE: accessing and scoring molecular interactions.

Nat Methods. 2011 Jun 29;8(7):528-9. doi: 10.1038/nmeth.1637.

The Bovine HapMap Consortium.

Genome wide survey of SNP variation uncovers the genetic structure of cattle breeds.

Science. 2009 Apr 24;324(5926):528-32. doi: 10.1126/science.1167936.

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