Tim is a research associate at the Climate Change Cluster with expertise in bioinformatics and computational biology. His research interest focusses on marine ecology, specifically on understanding the genetic and molecular bases of complex relationships between marine microbial organisms such as microalgae, bacteria and viruses.
After finishing his PhD at the Arctic University of Norway, Tromsø, Norway, in the field of bacterial comparative genomics and bioinformatics in 2013 Tim started a postdoc at CSIRO’s Oceans and Atmosphere Flagship in Tasmania where he joined the Environmental Genomics Team of Dr. Levente Bodrossy.
In 2016 Tim joined the Climate Change Cluster (C3) as a Research Associate where he works across the different research projects as the lead bioinformatician to strengthen bioinformatics capabilities at the C3.
Tim has applied his expertise in omics data analysis, e.g. comparative genomics, transcriptomics and metagenomics, in large scale projects such as the Ocean Sampling Day and the Australian Marine Microbes project.
Given the growing importance of computers and data analysis in biological sciences Tim is also providing bioinformatics support and training to researchers and students across the C3. He is applying an inclusive and open teaching philosophy that takes into account the challenges that many life scientists face when they are confronted with bioinformatics and dta analysis for the first time.
Can supervise: YES
- microbial genomics including microalgae, bacteria and viruses
- metagenomics / metatranscriptomics
- pathway reconstruction and systems biology
Lawson, C.A., Raina, J.-.B., Kahlke, T., Seymour, J.R. & Suggett, D.J. 2018, 'Defining the core microbiome of the symbiotic dinoflagellate, Symbiodinium.', Environmental microbiology reports, vol. 10, no. 1, pp. 7-11.View/Download from: UTS OPUS or Publisher's site
Dinoflagellates of the genus Symbiodinium underpin the survival and ecological success of corals. The use of cultured strains has been particularly important to disentangle the complex life history of Symbiodinium and their contribution to coral host physiology. However, these cultures typically harbour abundant bacterial communities which likely play important, but currently unknown, roles in Symbiodinium biology. We characterized the bacterial communities living in association with a wide phylogenetic diversity of Symbiodinium cultures (18 types spanning 5 clades) to define the core Symbiodinium microbiome. Similar to other systems, bacteria were nearly two orders of magnitude more numerically abundant than Symbiodinium cells and we identified three operational taxonomic units (OTUs) which were present in all cultures. These represented the -proteobacterium Labrenzia and the -proteobacteria Marinobacter and Chromatiaceae. Based on the abundance and functional potential of bacteria harboured in these cultures, their contribution to Symbiodinium physiology can no longer be ignored.
Goodwin, K.D., Thompson, L.R., Duarte, B., Kahlke, T., Thompson, A.R., Marques, J.C. & Caador, I. 2017, 'DNA sequencing as a tool to monitor marine ecological status', Frontiers in Marine Science, vol. 4, no. MAY.View/Download from: Publisher's site
© 2017 Goodwin, Thompson, Duarte, Kahlke, Thompson, Marques and Caador. Many ocean policies mandate integrated, ecosystem-based approaches to marine monitoring, driving a global need for efficient, low-cost bioindicators of marine ecological quality. Most traditional methods to assess biological quality rely on specialized expertise to provide visual identification of a limited set of specific taxonomic groups, a time-consuming process that can provide a narrow view of ecological status. In addition, microbial assemblages drive food webs but are not amenable to visual inspection and thus are largely excluded from detailed inventory. Molecular-based assessments of biodiversity and ecosystem function offer advantages over traditional methods and are increasingly being generated for a suite of taxa using a "microbes to mammals" or "barcodes to biomes" approach. Progress in these efforts coupled with continued improvements in high-throughput sequencing and bioinformatics pave the way for sequence data to be employed in formal integrated ecosystem evaluation, including food web assessments, as called for in the European Union Marine Strategy Framework Directive. DNA sequencing of bioindicators, both traditional (e.g., benthic macroinvertebrates, ichthyoplankton) and emerging (e.g., microbial assemblages, fish via eDNA), promises to improve assessment of marine biological quality by increasing the breadth, depth, and throughput of information and by reducing costs and reliance on specialized taxonomic expertise.
Jiang, Z., Kumar, M., Padula, M.P., Pernice, M., Kahlke, T., Kim, M. & Ralph, P.J. 2017, 'Development of an Efficient Protein Extraction Method Compatible with LC-MS/MS for Proteome Mapping in Two Australian Seagrasses Zostera muelleri and Posidonia australis.', Frontiers in Plant Science, vol. 8, pp. 1-14.View/Download from: UTS OPUS or Publisher's site
The availability of the first complete genome sequence of the marine flowering plant Zostera marina (commonly known as seagrass) in early 2016, is expected to significantly raise the impact of seagrass proteomics. Seagrasses are marine ecosystem engineers that are currently declining worldwide at an alarming rate due to both natural and anthropogenic disturbances. Seagrasses (especially species of the genus Zostera) are compromised for proteomic studies primarily due to the lack of efficient protein extraction methods because of their recalcitrant cell wall which is rich in complex polysaccharides and a high abundance of secondary metabolites in their cells. In the present study, three protein extraction methods that are commonly used in plant proteomics i.e., phenol (P); trichloroacetic acid/acetone/SDS/phenol (TASP); and borax/polyvinyl-polypyrrolidone/phenol (BPP) extraction, were evaluated quantitatively and qualitatively based on two dimensional isoelectric focusing (2D-IEF) maps and LC-MS/MS analysis using the two most abundant Australian seagrass species, namely Zostera muelleri and Posidonia australis. All three tested methods produced high quality protein extracts with excellent 2D-IEF maps in P. australis. However, the BPP method produces better results in Z. muelleri compared to TASP and P. Therefore, we further modified the BPP method (M-BPP) by homogenizing the tissue in a modified protein extraction buffer containing both ionic and non-ionic detergents (0.5% SDS; 1.5% Triton X-100), 2% PVPP and protease inhibitors. Further, the extracted proteins were solubilized in 0.5% of zwitterionic detergent (C7BzO) instead of 4% CHAPS. This slight modification to the BPP method resulted in a higher protein yield, and good quality 2-DE maps with a higher number of protein spots in both the tested seagrasses. Further, the M-BPP method was successfully utilized in western-blot analysis of phosphoenolpyruvate carboxylase (PEPC-a key enzyme for carbon metabolism). ...
McLaughlin, R.L., Schijven, D., van Rheenen, W., van Eijk, K.R., O'Brien, M., Kahn, R.S., Ophoff, R.A., Goris, A., Bradley, D.G., Al-Chalabi, A., van den Berg, L.H., Luykx, J.J., Hardiman, O., Veldink, J.H., Project MinE GWAS Consortium & Schizophrenia Working Group of the Psychiatric Genomics Consortium 2017, 'Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.', Nature communications, vol. 8, p. 14774.View/Download from: Publisher's site
We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P=1 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.
Kahle and Umbers introduce the ways by which organisms emit light though chemical reactions.
ten Hoopen, P., Amid, C., Buttigieg, P.L., Pafilis, E., Bravakos, P., Cerdeño-Tárraga, A.M., Gibson, R., Kahlke, T., Legaki, A., Narayana Murthy, K., Papastefanou, G., Pereira, E., Rossello, M., Luisa Toribio, A. & Cochrane, G. 2016, 'Value, but high costs in post-deposition data curation.', Database : the journal of biological databases and curation, vol. 2016.View/Download from: UTS OPUS or Publisher's site
Discoverability of sequence data in primary data archives is proportional to the richness of contextual information associated with the data. Here, we describe an exercise in the improvement of contextual information surrounding sample records associated with metagenomics sequence reads available in the European Nucleotide Archive. We outline the annotation process and summarize findings of this effort aimed at increasing usability of publicly available environmental data. Furthermore, we emphasize the benefits of such an exercise and detail its costs. We conclude that such a third party annotation approach is expensive and has value as an element of curation, but should form only part of a more sustainable submitter-driven approach. Database URL: http://www.ebi.ac.uk/ena.
Williamson, A., Hjerde, E. & Kahlke, T. 2016, 'Analysis of the distribution and evolution of the ATP-dependent DNA ligases of bacteria delineates a distinct phylogenetic group 'Lig E'.', Molecular microbiology, vol. 99, no. 2, pp. 274-290.View/Download from: UTS OPUS or Publisher's site
Prior to the discovery of a minimal ATP-dependent DNA ligase in Haemophilus influenzae, bacteria were thought to only possess a NAD-dependent ligase, which was involved in sealing of Okazaki fragments. We now know that a diverse range of bacterial species possess up to six of these accessory bacterial ATP-dependent DNA ligases (b-ADLs), which vary in size and enzymatic domain associations. Here we compare the domain structure of different types of b-ADLs and investigate their distribution among the bacterial domain to describe possible evolutionary trajectories that gave rise to the sequence and structural diversity of these enzymes. Previous biochemical and genetic analyses have delineated three main classes of these enzymes: Lig B, Lig C and Lig D, which appear to have descended from a common ancestor within the bacterial domain. In the present study, we delineate a fourth group of b-ADLs, Lig E, which possesses a number of unique features at the primary and tertiary structural levels. The biochemical characteristics, domain structure and inferred extracellular location sets this group apart from the other b-ADLs. The results presented here indicate that the Lig E type ligases were horizontally transferred into bacteria in a separate event from other b-ADLs possibly from a bacteriophage.
Thode, S.K., Kahlke, T., Robertsen, E.M., Hansen, H. & Haugen, P. 2015, 'The immediate global responses of Aliivibrio salmonicida to iron limitations.', BMC microbiology, vol. 15, p. 9.View/Download from: UTS OPUS or Publisher's site
Iron is an essential micronutrient for all living organisms, and virulence and sequestration of iron in pathogenic bacteria are believed to be correlated. As a defence mechanism, potential hosts therefore keep the level of free iron inside the body to a minimum. In general, iron metabolism is well studied for some bacteria (mostly human or animal pathogens). However, this area is still under-investigated for a number of important bacterial pathogens. Aliivibrio salmonicida is a fish pathogen, and previous studies of this bacterium have shown that production of siderophores is temperature regulated and dependent on low iron conditions. In this work we studied the immediate changes in transcription in response to a sudden decrease in iron levels in cultures of A. salmonicida. In addition, we compared our results to studies performed with Vibrio cholerae and Vibrio vulnificus using a pan-genomic approach.Microarray technology was used to monitor global changes in transcriptional levels. Cultures of A. salmonicida were grown to mid log phase before the iron chelator 2,2'-dipyridyl was added and samples were collected after 15 minutes of growth. Using our statistical cut-off values, we retrieved thirty-two differentially expressed genes where the most up-regulated genes belong to an operon encoding proteins responsible for producing the siderophore bisucaberin. A subsequent pan-transcriptome analysis revealed that nine of the up-regulated genes from our dataset were also up-regulated in datasets from similar experiments using V. cholerae and V. vulnificus, thus indicating that these genes are involved in a shared strategy to mitigate low iron conditions.The present work highlights the effect of iron limitation on the gene regulatory network of the fish pathogen A. salmonicida, and provides insights into common and unique strategies of Vibrionaceae species to mitigate low iron conditions.
Cavanagh, J.P., Hjerde, E., Holden, M.T.G., Kahlke, T., Klingenberg, C., Flægstad, T., Parkhill, J., Bentley, S.D. & Sollid, J.U.E. 2014, 'Whole-genome sequencing reveals clonal expansion of multiresistant Staphylococcus haemolyticus in European hospitals.', The Journal of antimicrobial chemotherapy, vol. 69, no. 11, pp. 2920-2927.View/Download from: UTS OPUS or Publisher's site
Staphylococcus haemolyticus is an emerging cause of nosocomial infections, primarily affecting immunocompromised patients. A comparative genomic analysis was performed on clinical S. haemolyticus isolates to investigate their genetic relationship and explore the coding sequences with respect to antimicrobial resistance determinants and putative hospital adaptation.Whole-genome sequencing was performed on 134 isolates of S. haemolyticus from geographically diverse origins (Belgium, 2; Germany, 10; Japan, 13; Norway, 54; Spain, 2; Switzerland, 43; UK, 9; USA, 1). Each genome was individually assembled. Protein coding sequences (CDSs) were predicted and homologous genes were categorized into three types: Type I, core genes, homologues present in all strains; Type II, unique core genes, homologues shared by only a subgroup of strains; and Type III, unique genes, strain-specific CDSs. The phylogenetic relationship between the isolates was built from variable sites in the form of single nucleotide polymorphisms (SNPs) in the core genome and used to construct a maximum likelihood phylogeny.SNPs in the genome core regions divided the isolates into one major group of 126 isolates and one minor group of isolates with highly diverse genomes. The major group was further subdivided into seven clades (A-G), of which four (A-D) encompassed isolates only from Europe. Antimicrobial multiresistance was observed in 77.7% of the collection. High levels of homologous recombination were detected in genes involved in adherence, staphylococcal host adaptation and bacterial cell communication.The presence of several successful and highly resistant clones underlines the adaptive potential of this opportunistic pathogen.
Kahlke, T. & Thorvaldsen, S. 2012, 'Molecular characterization of cold adaptation of membrane proteins in the Vibrionaceae core-genome.', PloS one, vol. 7, no. 12, p. e51761.View/Download from: UTS OPUS or Publisher's site
Cold-adaptation strategies have been studied in multiple psychrophilic organisms, especially for psychrophilic enzymes. Decreased enzyme activity caused by low temperatures as well as a higher viscosity of the aqueous environment require certain adaptations to the metabolic machinery of the cell. In addition to this, low temperature has deleterious effects on the lipid bilayer of bacterial membranes and therefore might also affect the embedded membrane proteins. Little is known about the adaptation of membrane proteins to stresses of the cold. In this study we investigate a set of 66 membrane proteins from the core genome of the bacterial family Vibrionaceae to identify general characteristics that discern psychrophilic and mesophilic membrane proteins. Bioinformatical and statistical methods were used to analyze the alignments of the three temperature groups mesophilic, intermediate and psychrophilic. Surprisingly, our results show little or no adaptation to low temperature for those parts of the proteins that are predicted to be inside the membrane. However, changes in amino acid composition and hydrophobicity are found for complete sequences and sequence parts outside the lipid bilayer. Among others, the results presented here indicate a preference for helix-breaking and destabilizing amino acids Ile, Asp and Thr and an avoidance of the helix-forming amino acid Ala in the amino acid composition of psychrophilic membrane proteins. Furthermore, we identified a lower overall hydrophobicity of psychrophilic membrane proteins in comparison to their mesophilic homologs. These results support the stability-flexibility hypothesis and link the cold-adaptation strategies of membrane proteins to those of loop regions of psychrophilic enzymes.
Kahlke, T., Goesmann, A., Hjerde, E., Willassen, N.P. & Haugen, P. 2012, 'Unique core genomes of the bacterial family vibrionaceae: insights into niche adaptation and speciation.', BMC genomics, vol. 13, p. 179.View/Download from: UTS OPUS or Publisher's site
BACKGROUND: The criteria for defining bacterial species and even the concept of bacterial species itself are under debate, and the discussion is apparently intensifying as more genome sequence data is becoming available. However, it is still unclear how the new advances in genomics should be used most efficiently to address this question. In this study we identify genes that are common to any group of genomes in our dataset, to determine whether genes specific to a particular taxon exist and to investigate their potential role in adaptation of bacteria to their specific niche. These genes were named unique core genes. Additionally, we investigate the existence and importance of unique core genes that are found in isolates of phylogenetically non-coherent groups. These groups of isolates, that share a genetic feature without sharing a closest common ancestor, are termed genophyletic groups. RESULTS: The bacterial family Vibrionaceae was used as the model, and we compiled and compared genome sequences of 64 different isolates. Using the software orthoMCL we determined clusters of homologous genes among the investigated genome sequences. We used multilocus sequence analysis to build a host phylogeny and mapped the numbers of unique core genes of all distinct groups of isolates onto the tree. The results show that unique core genes are more likely to be found in monophyletic groups of isolates. Genophyletic groups of isolates, in contrast, are less common especially for large groups of isolate. The subsequent annotation of unique core genes that are present in genophyletic groups indicate a high degree of horizontally transferred genes. Finally, the annotation of the unique core genes of Vibrio cholerae revealed genes involved in aerotaxis and biosynthesis of the iron-chelator vibriobactin. CONCLUSION: The presented work indicates that genes specific for any taxon inside the bacterial family Vibrionaceae exist. These unique core genes encode conserved metabolic funct...
Dondrup, M., Albaum, S.P., Griebel, T., Henckel, K., Jünemann, S., Kahlke, T., Kleindt, C.K., Küster, H., Linke, B., Mertens, D., Mittard-Runte, V., Neuweger, H., Runte, K.J., Tauch, A., Tille, F., Pühler, A. & Goesmann, A. 2009, 'EMMA 2--a MAGE-compliant system for the collaborative analysis and integration of microarray data.', BMC bioinformatics, vol. 10, p. 50.View/Download from: Publisher's site
BACKGROUND: Understanding transcriptional regulation by genome-wide microarray studies can contribute to unravel complex relationships between genes. Attempts to standardize the annotation of microarray data include the Minimum Information About a Microarray Experiment (MIAME) recommendations, the MAGE-ML format for data interchange, and the use of controlled vocabularies or ontologies. The existing software systems for microarray data analysis implement the mentioned standards only partially and are often hard to use and extend. Integration of genomic annotation data and other sources of external knowledge using open standards is therefore a key requirement for future integrated analysis systems. RESULTS: The EMMA 2 software has been designed to resolve shortcomings with respect to full MAGE-ML and ontology support and makes use of modern data integration techniques. We present a software system that features comprehensive data analysis functions for spotted arrays, and for the most common synthesized oligo arrays such as Agilent, Affymetrix and NimbleGen. The system is based on the full MAGE object model. Analysis functionality is based on R and Bioconductor packages and can make use of a compute cluster for distributed services. CONCLUSION: Our model-driven approach for automatically implementing a full MAGE object model provides high flexibility and compatibility. Data integration via SOAP-based web-services is advantageous in a distributed client-server environment as the collaborative analysis of microarray data is gaining more and more relevance in international research consortia. The adequacy of the EMMA 2 software design and implementation has been proven by its application in many distributed functional genomics projects. Its scalability makes the current architecture suited for extensions towards future transcriptomics methods based on high-throughput sequencing approaches which have much higher computational requirements than microarrays.