Michele is a core member of the Algal Biosystems and Biotechnology group in the Climate Change Cluster (C3) at UTS.
Michele is a molecular biologist specialised in the investigation of the genetics and biochemistry of microalgae, unicellular photosynthetic eukaryotes. Through metabolic engineering and synthetic biology, his research focuses at harnessing their unique potential to manufacture high-value bio-products.
In 2017 Michele was awarded a CSIRO Synthetic Biology Future Science Platform Fellowship to work on diatom synthetic biology.
Michele joined C3:UTS in 2014, contributing to establishing a platform for microalgal molecular biotechnology, to explore the potential of microalgae as cell-sized factories for the production of a wide range of high-value bio-products.
Prior to joining C3, Michele completed his Ph.D. in Biotechnology and Biochemistry at Ghent University (Belgium), in the VIB-UGent Center for Plant Systems Biology, where he worked on the reconstruction of diatom and plant genome-scale metabolic networks, and characterised novel aspects of diatom carbohydrate and terpenoid metabolism.
2017 CSIRO Synthetic Biology Future Science Platform Fellowship
Australia-New Zealand Marine Biotechnology Society
Synthetic Biology Australasia
Can supervise: YES
- Algal and plant terpenoid metabolism
- Algae and plant molecular biology and genetics
- Algal strain engineering
- Algal biotechnology
- Synthetic biology
- Metabolic engineering
Lead demonstrator in "Marine Productivity and Climate Change" UTS
Guest Lecturer in "Environmental Biotechnology", UTS
Terpenoids are a group of natural products that have a variety of roles, both essential and non-essential, in metabolism and in biotic and abiotic interactions, as well as commercial applications such as pharmaceuticals, food additives, and chemical feedstocks. Economic viability for commercial applications is commonly not achievable by using natural source organisms or chemical synthesis. Engineered bio-production in suitable heterologous hosts is often required to achieve commercial viability. However, our poor understanding of regulatory mechanisms and other biochemical processes makes obtaining efficient conversion yields from feedstocks challenging. Moreover, production from carbon dioxide via photosynthesis would significantly increase the environmental and potentially the economic credentials of these processes by disintermediating biomass feedstocks. In this paper, we briefly review terpenoid metabolism, outline some recent advances in terpenoid metabolic engineering, and discuss why photosynthetic unicellular organisms-such as algae and cyanobacteria-might be preferred production platforms for the expression of some of the more challenging terpenoid pathways.
Pollier, J, Vancaester, E, Kuzhiumparambil, U, Vickers, CE, Vandepoele, K, Goossens, A & Fabris, M 2018, 'A widespread alternative squalene epoxidase participates in eukaryote steroid biosynthesis.', Nature Microbiology.View/Download from: Publisher's site
Steroids are essential triterpenoid molecules that are present in all eukaryotes and modulate the fluidity and flexibility of cell membranes. Steroids also serve as signalling molecules that are crucial for growth, development and differentiation of multicellular organisms1-3. The steroid biosynthetic pathway is highly conserved and is key in eukaryote evolution4-7. The flavoprotein squalene epoxidase (SQE) catalyses the first oxygenation reaction in this pathway and is rate limiting. However, despite its conservation in animals, plants and fungi, several phylogenetically widely distributed eukaryote genomes lack an SQE-encoding gene7,8. Here, we discovered and characterized an alternative SQE (AltSQE) belonging to the fatty acid hydroxylase superfamily. AltSQE was identified through screening of a gene library of the diatom Phaeodactylum tricornutum in a SQE-deficient yeast. In accordance with its divergent protein structure and need for cofactors, we found that AltSQE is insensitive to the conventional SQE inhibitor terbinafine. AltSQE is present in many eukaryotic lineages but is mutually exclusive with SQE and shows a patchy distribution within monophyletic clades. Our discovery provides an alternative element for the conserved steroid biosynthesis pathway, raises questions about eukaryote metabolic evolution and opens routes to develop selective SQE inhibitors to control hazardous organisms.
Matthijs, M, Fabris, M, Obata, T, Foubert, I, Franco-Zorrilla, MJ, Solano, R, Fernie, AF, Vyverman, W & Goossens, A 2017, 'The transcription factor bZIP14 regulates the TCA cycle in the diatom Phaeodactylum tricornutum', EMBO Journal, vol. 36, no. 11, pp. 1559-1576.View/Download from: UTS OPUS or Publisher's site
Diatoms are amongst the most important marine microalgae in terms of biomass, but little is known concerning the molecular mechanisms that regulate their versatile metabolism. Here, the pennate diatom Phaeodactylum tricornutum was studied at the metabolite and transcriptome level during nitrogen starvation and following imposition of three other stresses that impede growth. The coordinated upregulation of the tricarboxylic acid (TCA) cycle during the nitrogen stress response was the most striking observation. Through coexpression analysis and DNA binding assays, the transcription factor bZIP14 was identified as a regulator of the TCA cycle, also beyond the nitrogen starvation response, namely in diurnal regulation. Accordingly, metabolic and transcriptional shifts were observed upon overexpression of bZIP14 in transformed P. tricornutum cells. Our data indicate that the TCA cycle is a tightly regulated and important hub for carbon reallocation in the diatom cell during nutrient starvation and that bZIP14 is a conserved regulator of this cycle.
Kim, J, Fabris, M, Baart, G, Kim, MK, Goossens, A, Vyverman, W, Falkowski, P & Lun, DS 2016, 'Flux balance analysis of primary metabolism in the diatom Phaeodactylum tricornutum', The Plant Journal, vol. 85, no. 1, pp. 161-176.View/Download from: UTS OPUS or Publisher's site
Diatoms (Bacillarophyceae) are photosynthetic unicellular microalgae that have risen to ecological prominence in the modern oceans over the past 30 million years. They are of interest as potential feedstocks for sustainable biofuels. Maximizing production of these feedstocks will likely require genetic modifications and an understanding of algal metabolism. These processes can benefit from genome-scale models, which predict intracellular fluxes and theoretical yields, as well as the viability of knockout and knockin transformants. Here we present a genome-scale metabolic model of a fully sequenced and transformable diatom, Phaeodactylum tricornutum. The metabolic network was constructed using the P. tricornutum genome, biochemical literature, and online bioinformatic databases. Intracellular fluxes in P. tricornutum were calculated for autotrophic, mixotrophic, and heterotrophic growth conditions, as well as knockout conditions that explore the in silico role of glycolytic enzymes in the mitochondrion. The flux distribution of lower glycolysis in the mitochondrion depended on which transporters for TCA metabolites were included in the model. The growth rate predictions were validated with experimental data using chemostats. Two published studies on this organism (Bailleul et al., 2015, Zheng et al., 2013) were used to validate model predictions for cyclic electron flow under autotrophic conditions, and fluxes through the phosphoketolase, glycine and serine synthesis pathways under mixotrophic conditions. Several gaps in annotation were also identified. The model also explored unusual features of diatom metabolism, such as the presence of lower glycolysis in the mitochondrion, as well as differences between P. tricornutum and other photosynthetic organisms.
Matthijs, M, Fabris, M, Broos, S, Vyverman, W & Goossens, A 2016, 'Profiling of the Early Nitrogen Stress Response in the Diatom Phaeodactylum Tricornutum Reveals a Novel Family of RING-Domain Transcription Factors', Plant Physiology, vol. 170, no. 1, pp. 489-498.View/Download from: UTS OPUS or Publisher's site
Diatoms often inhabit highly variable habitats where they are confronted with a wide variety of stresses, frequently including starvation of nutrients such as nitrogen. In this study, the transcriptome of the model diatom Phaeodactylum tricornutum was profiled during the onset of nitrogen starvation by RNA-sequencing and overrepresented motifs were determined in promoters of genes that were early and strongly upregulated during the nitrogen stress response. One of these motifs could be bound by a nitrogen starvation-inducible RING-domain protein termed RING-GAF-Glutamine containing protein (RGQ1), which was shown to act as a transcription factor and belongs to a previously uncharacterized family that is conserved in heterokont algae.
Murray, SA, Suggett, DJ, Seymour, JR, Doblin, M, Kohli, GS, Fabris, M & Ralph, PJ 2016, 'Unravelling the functional genetics of dinoflagellates: a review of approaches and opportunities', Perspectives in Phycology, vol. 3, no. 1, pp. 37-52.View/Download from: UTS OPUS or Publisher's site
Dinoflagellates occupy an extraordinarily diverse array of ecological niches. Their success stems from a suite of functional and ecological strategies, including the production of secondary metabolites with anti-predator or allelopathic impacts, nutritional flexibility, and the ability to form symbiotic relationships. Despite their ecological importance, we currently have a poor understanding of the genetic basis for many of these strategies, due to the complex genomes of dinoflagellates. Genomics and transcriptomic sequencing approaches are now providing the first insights into the genetic basis of some dinoflagellate functional traits, providing the opportunity for novel ecological experiments, novel methods for monitoring of harmful biotoxins, and allowing us to investigate the production of ecologically and economically important compounds such as the long chain polyunsaturated fatty acid, docosahexanoic acid and the climatically important metabolite, dimethylsulfoniopropionate. Despite these advances, we still generally lack the ability to genetically manipulate species, which would enable the confirmation of biosynthetic pathways and the development of novel bio-engineering applications. Here, we describe advances in understanding the genetic basis of dinoflagellate ecology, and propose biotechnological approaches that could be applied to further transform our understanding of this unique group of eukaryotes.
Fabris, M, Matthijs, M, Carbonelle, S, Moses, T, Pollier, J, Dasseville, R, Baart, GJE, Vyverman, W & Goossens, A 2014, 'Tracking the sterol biosynthesis pathway of the diatom Phaeodactylum tricornutum', New Phytologist, vol. 204, no. 3, pp. 521-535.View/Download from: UTS OPUS or Publisher's site
Diatoms are unicellular photosynthetic microalgae that play a major role in global primaryproduction and aquatic biogeochemical cycling. Endosymbiotic events and recurrent genetransfers uniquely shaped the genome of diatoms, which contains features from severaldomains of life. The biosynthesis pathways of sterols, essential compounds in all eukaryoticcells, and many of the enzymes involved are evolutionarily conserved in eukaryotes. Althoughwell characterized in most eukaryotes, the pathway leading to sterol biosynthesis in diatomshas remained hitherto unidentified.Through the DiatomCyc database we reconstructed the mevalonate and sterol biosyntheticpathways of the model diatom Phaeodactylum tricornutum in silico. We experimentally veri-fied the predicted pathways using enzyme inhibitor, gene silencing and heterologous geneexpression approaches.Our analysis revealed a peculiar, chimeric organization of the diatom sterol biosynthesispathway, which possesses features of both plant and fungal pathways. Strikingly, it lacks aconventional squalene epoxidase and utilizes an extended oxidosqualene cyclase and a multi-functional isopentenyl diphosphate isomerase/squalene synthase enzyme.The reconstruction of the P. tricornutum sterol pathway underscores the metabolic plastic-ity of diatoms and offers important insights for the engineering of diatoms for sustainable pro-duction of biofuels and high-value chemicals.
Van Moerkercke, A, Fabris, M, Pollier, J, Baart, GJE, Rombauts, S, Hasnain, G, Rischer, H, Memelink, J, Oksman-Caldentey, K-M & Goossens, A 2013, 'CathaCyc, a Metabolic Pathway Database Built from Catharanthus roseus RNA-Seq Data', PLANT AND CELL PHYSIOLOGY, vol. 54, no. 5, pp. 673-685.View/Download from: UTS OPUS or Publisher's site
Fabris, M, Matthijs, M, Rombauts, S, Vyverman, W, Goossens, A & Baart, GJE 2012, 'The metabolic blueprint of Phaeodactylum tricornutum reveals a eukaryotic Entner-Doudoroff glycolytic pathway', Plant Journal, vol. 70, no. 6, pp. 1004-1014.View/Download from: UTS OPUS or Publisher's site
Diatoms are one of the most successful groups of unicellular eukaryotic algae. Successive endosymbiotic events contributed to their flexible metabolism, making them competitive in variable aquatic habitats. Although the recently sequenced genomes of the model diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana have provided the first insights into their metabolic organization, the current knowledge on diatom biochemistry remains fragmentary. By means of a genome-wide approach, we developed DiatomCyc, a detailed pathway/genome database of P. tricornutum. DiatomCyc contains 286 pathways with 1719 metabolic reactions and 1613 assigned enzymes, spanning both the central and parts of the secondary metabolism of P. tricornutum. Central metabolic pathways, such as those of carbohydrates, amino acids and fatty acids, were covered. Furthermore, our understanding of the carbohydrate model in P. tricornutum was extended. In particular we highlight the discovery of a functional Entner–Doudoroff pathway, an ancient alternative for the glycolytic Embden–Meyerhof–Parnas pathway, and a putative phosphoketolase pathway, both uncommon in eukaryotes. DiatomCyc is accessible online (http://www.diatomcyc.org), and offers a range of software tools for the visualization and analysis of metabolic networks and 'omics' data. We anticipate that DiatomCyc will be key to gaining further understanding of diatom metabolism and, ultimately, will feed metabolic engineering strategies for the industrial valorization of diatoms.
A/Prof Claudia Vickers (AIBN-UQ/CSIRO)
Prof. Alain Goossens (VIB-UGent Centre for Plant Systems Biology)
CSIRO Synthetic Biology Future Science Platform