Dacks (Ph.D. Dalhousie University)
Department of Cell Biology
5-31 Medical Sciences Building
Phone: (780) 248-1493
Fax: (780) 492-0450 (fax)
- Canada Research Chair in Evolutionary Cell Biology
The membrane-trafficking system is a key characteristic of eukaryotes (humans, plants, yeast, etc.) and one of the defining features that separates us from bacteria at a cellular level. It is responsible for the proper movement and final location of most of the material in our cells. It underlies not only brain activity, and hormone secretion in humans, but healthy plant growth, as well as normal cellular activity in a diverse array of single-celled organisms important for our economy, our environment and our health. The pathogenic mechanisms of many parasites, such as the organisms causing malaria, primary amoebic meningoencephalitis and African sleeping sickness, are all underpinned by action of the membrane-trafficking system.
Evidence suggests that the membrane-trafficking system arose early on in eukaryotic evolution, with the major protein families involved likely having been already present in our ancestors over one billion years ago. The innovation of an endomembrane system would have been crucial for early eukaryotes, allowing predation, surface remodelling and increased cell size.
The long-term goal of my research program is to understand the evolution and diversity of the eukaryotic membrane-trafficking system.
Although evolutionary in nature, my research also provides insight into basic cell biology, parasitism and pathogenesis. By comparative genomics and evolutionary cell biology addressing organisms from across the taxonomic breadth of eukaryotes (beyond yeast to man), core components of eukaryotic cellular systems are identified. This allows the development of models of cell biological mechanism that are valid for all eukaryotic cells. It is also possible to place in context some aspects that are unique to a particular model system. Features that are unique, when found in parasitic protistan pathogens, may represent potential therapeutic targets.
We use genomics and molecular evolutionary tools such as phylogenetics and homology searching to address our questions. Some of our analyses involve searching publically available genome data. Additionally, the lab is currently involved in several international sequencing projects of protist genomes to examine their membrane trafficking machinery (Monocercomonoides sp., Trimastix pyriformis, Blastocystis homonis and more), having just been involved in the successful publication of the Emiliania huxleyi, Guillardia theta, Bigelowiella natans, and Naegleria gruberi genomes.
Three interconnected lines of research are currently on-going in my lab:
Origin and evolution of the membrane trafficking system
Detailed evolutionary studies of individual protein families (eg. SNAREs, vesicle coats) can reveal important information about the specific history of that membrane-trafficking machinery and about the membrane-trafficking system in general. Such studies have thus far demonstrated ancient complexity in the trafficking system and the proposal of an evolutionary mechanism for non-endosymbiotic organelle evolution. As a by-product of these investigations, we have uncovered new protein complexes and trafficking pathways, even in human cells and revealed the cryptic origin of others relevant to neurodegenerative diseases. We continue to investigate the evolution of protein families involved in membrane-trafficking, with the goal of understanding the emergence of specificity and organelle identity in the eukaryotic cell.
Some of the world’s most significant infectious diseases are caused by microbial eukaryotes. Our work investigates the ways in which the cell biology of membrane-trafficking, as we understand it primarily from studies in animal and yeast models, applies to that of organisms that cause significant mortality and poverty across the world. We often collaboratively pair our in silico work with molecular cell biology to test hypotheses. Current work includes molecular evolutionary work on Trypanosoma brucei (African Sleeping Sickness) and evolution of invasion organelles in Apicomplexa (malaria, toxoplasmosis). We are also among research groups leading the genome sequencing project of Naegleria fowleri (the brain-eating amoeba).
Furthermore, I am the co-founder and co-director of the (UAlberta) Biomedical Global Health Research Network. The goal of the network is to facilitate interaction between UAlberta researchers doing biomedical work with relevance to, and in aid of, Global Health.
Microbial eukaryotes and the oilsands
The Northern Alberta oil sands are one of the biggest deposits of bitumen in the world, extending over 77,000 km2 and are a reserve of comparable magnitude to the world’s reserves of conventional petroleum. Over 120 000 Albertans are directly employed in mining and oil extraction sectors, not to mention the industries supporting these jobs. The oil sands therefore have both local and global significance as energy reservoirs and economic drivers. Responsible development of these petrochemical resources is an important priority for the wellbeing of Albertans.
However, exploitation of the oilsands is also a source of environmental concern. Tailings ponds contain the wastes from processing surface-mined oil sands ores. Compounds such as naphthenic acids, and polyaromatic hydrocarbons are known components of the ponds and have toxic effects, while experimental exposure to oilsands process-affected water has been shown to be directly toxic in mouse models. Soils overlying bitumen deposits are also disrupted during surface mining and so restoring them to functioning ecosystems is also important. Reclamation should therefore be an environmental and health priority for Alberta.
Several strategies for conversion of the tailings ponds and soils into viable landscapes have been proposed, with microbial communities playing a biological role in establishing ecosystem health. There has been extensive study of the prokaryotic communities of the tailings ponds, showing both beneficial and adverse effects in situ. However, little work has been done on the microbial eukaryotic communities and none using modern molecular methods. This despite the influence in all other environments tested for microbial eukaryotes in food webs impacting both the prokaryotic communities and upwards into animals and plants. Additionally, work in other petrochemical-impacted environments has shown changes in both the community structure (who and how many) and in the cell biology of individual microbial eukaryotic organisms.
We have recently launched investigations into the potential role of microbial eukaryotes in tailings ponds and oil sand associated soils. This work has implications for environmental reclamation, and for organism discovery in anthropogenically disturbed environments.
Selected peer-reviewed publications (* denotes equal contribution, **denotes JBD as corresponding author, trainees underlined, visiting scientists underlined and italicized)
Origin and evolution of the membrane trafficking system.
Hirst J*, Schlacht A*, Norcott JP, Traynor D, Bloomfield G, Antrobus R, Kay RR, Dacks JB**, Robinson MS. Characterization of TSET, an ancient and widespread membrane trafficking complex. eLife. 2014 May 27;3:e02866.
Mast FD, Barlow LD, Rachubinski RA and Dacks JB**. “Evolutionary Mechanisms of Cellular complexity” (2014) Trends in Cell Biology pii: S0962-8924(14)00032-4.
Schlacht A, Herman EK, Klute MJ, Field MC and Dacks JB** “Missing pieces of an ancient puzzle: Evolution of the eukaryotic membrane-trafficking system” (2014) Cold Spring Harb Perspect Biol.
Elias M, Brighouse A, Gabernet-Castello C, Field MC, Dacks JB**. Sculpting the endomembrane system in deep time: high resolution phylogenetics of Rab GTPases. J Cell Sci. 2012 May 15;125(Pt 10):2500-8. doi: 10.1242/jcs.101378.
Hirst J, Barlow LD, Francisco GC, Sahlender DA, Seaman MN, Dacks JB**, Robinson MS. The fifth adaptor protein complex. PLoS Biol. 2011 Oct;9(10):e1001170. doi: 10.1371/journal.pbio.1001170.
Mowbrey K, Dacks JB**. Evolution and diversity of the Golgi body. FEBS Lett. 2009 Dec 3;583(23):3738-45. doi:10.1016/j.febslet.2009.10.025.
Field MC, Dacks JB. First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes. Curr Opin Cell Biol. 2009 Feb;21(1):4-13.doi: 10.1016/j.ceb.2008.12.004.
Dacks JB**, Poon PP, Field MC. Phylogeny of endocytic components yields insight into the process of nonendosymbiotic organelle evolution. Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):588-93. doi: 10.1073/pnas.0707318105.
Dacks JB**, Field MC. Evolution of the eukaryotic membrane-trafficking system: origin, tempo and mode. J Cell Sci. 2007 Sep 1;120(Pt 17):2977-85.
Murungi E, Barlow LD, Venkatesh D, Adunga V, Dacks JB**, Field MC, Christoffels, A. “A comparative analysis of trypanosomatid SNARE proteins” Parasitology International. (2014) 63(2):341-8.
Klinger CM, Klute MJ, Dacks JB** Comparative Genomic Analysis of Multi-subunit Tethering Complexes Demonstrates an Ancient Pan-Eukaryotic Complement and Sculpting in Apicomplexa. PLoS One. 2013 Sep 27;8(9):e76278
Klinger CM, Nisbet RE, Ouologuem DT, Roos DS, Dacks JB**. Cryptic organelle homology in apicomplexan parasites: insights from evolutionary cell biology. Curr Opin Microbiol. 2013 Aug;16(4):424-31. doi: 10.1016/j.mib.2013.07.015.
Herman EK, Greninger AL, Visvesvara GS, Marciano-Cabral F, Dacks JB**, Chiu CY. The mitochondrial genome and a 60-kb nuclear DNA segment from Naegleria fowleri, the causative agent of primary amoebic meningoencephalitis. J Eukaryot Microbiol.2013 Mar-Apr;60(2):179-91. doi: 10.1111/jeu.12022.
Koumandou VL, Klute MJ, Herman EK, Nunez-Miguel R, Dacks JB**, Field MC. Evolutionary reconstruction of the retromer complex and its function in Trypanosoma brucei. J Cell Sci. 2011 May 1;124(Pt 9):1496-509. doi:10.1242/jcs.081596.
Nevin WD, Dacks JB**. Repeated secondary loss of adaptin complex genes in the Apicomplexa. Parasitol Int. 2009 Mar;58(1):86-94. doi:10.1016/j.parint.2008.12.002.
Microbial Eukaryotic Genomics
Read BA, Kegel J, Klute MJ, Kuo A, Lefebvre SC, Maumus F, Mayer C, Miller J,Monier A, Salamov A, Young J, Aguilar M, Claverie JM, Frickenhaus S, Gonzalez K, Herman EK, Lin YC, Napier J, Ogata H, Sarno AF, Shmutz J, Schroeder D, de Vargas C, Verret F, von Dassow P, Valentin K, Van de Peer Y, Wheeler G; Emiliania huxleyi Annotation Consortium, Dacks JB*, Delwiche CF*, Dyhrman ST*, Glöckner G*, John U*, Richards T*, Worden AZ*, Zhang X*, Grigoriev IV. Pan genome of the phytoplankton Emiliania underpins its global distribution. Nature. 2013 Jul 11;499(7457):209-13. doi:10.1038/nature12221.
Curtis BA, Tanifuji G, Burki F, Gruber A, Irimia M, Maruyama S, Arias MC, Ball SG, Gile GH, Hirakawa Y, Hopkins JF, Kuo A, Rensing SA, Schmutz J, Symeonidi A, Elias M, Eveleigh RJ, Herman EK, Klute MJ, Nakayama T, Oborník M, Reyes-Prieto A, Armbrust EV, Aves SJ, Beiko RG, Coutinho P, Dacks JB, Durnford DG, Fast NM, Green BR, Grisdale CJ, Hempel F, Henrissat B, Höppner MP, Ishida K, Kim E, Kořený L, Kroth PG, Liu Y, Malik SB, Maier UG, McRose D, Mock T, Neilson JA, Onodera NT, Poole AM, Pritham EJ, Richards TA, Rocap G, Roy SW, Sarai C, Schaack S, Shirato S, Slamovits CH, Spencer DF, Suzuki S, Worden AZ, Zauner S, Barry K, Bell C, Bharti AK, Crow JA, Grimwood J, Kramer R, Lindquist E, Lucas S, Salamov A, McFadden GI, Lane CE, Keeling PJ, Gray MW, Grigoriev IV, Archibald JM. Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs. Nature. 2012 Dec 6;492(7427):59-65.doi:10.1038/nature11681.
Fritz-Laylin LK, Prochnik SE, Ginger ML, Dacks JB, Carpenter ML, Field MC, Kuo A, Paredez A, Chapman J, Pham J, Shu S, Neupane R, Cipriano M, Mancuso J, Tu H, Salamov A, Lindquist E, Shapiro H, Lucas S, Grigoriev IV, Cande WZ, Fulton C, Rokhsar DS, Dawson SC. The genome of Naegleria gruberi illuminates early eukaryotic versatility. Cell. 2010 Mar 5;140(5):631-42. doi:10.1016/j.cell.2010.01.032.
Carlton JM, Hirt RP, Silva JC, Delcher AL, Schatz M, Zhao Q, Wortman JR, Bidwell SL, Alsmark UC, Besteiro S, Sicheritz-Ponten T, Noel CJ, Dacks JB, Foster PG, Simillion C, Van de Peer Y, Miranda-Saavedra D, Barton GJ, Westrop GD, Müller S, Dessi D, Fiori PL, Ren Q, Paulsen I, Zhang H, Bastida-Corcuera FD, Simoes-Barbosa A, Brown MT, Hayes RD, Mukherjee M, Okumura CY, Schneider R, Smith AJ, Vanacova S, Villalvazo M, Haas BJ, Pertea M, Feldblyum TV, Utterback TR, Shu CL, Osoegawa K, de Jong PJ, Hrdy I, Horvathova L, Zubacova Z, Dolezal P, Malik SB, Logsdon JM Jr, Henze K, Gupta A, Wang CC, Dunne RL, Upcroft JA, Upcroft P, White O, Salzberg SL, Tang P, Chiu CH, Lee YS, Embley TM, Coombs GH, Mottram JC, Tachezy J, Fraser-Liggett CM, Johnson PJ. Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Science. 2007 Jan 12;315(5809):207-12.
Dr. María Inmaculada Ramírez Macías