Baum, Jake - Imperial College London - Department of Life Sciences, Biochemistry and Biotechnology

个人简介

Throughout its complex lifecycle the malaria parasites, from the genus Plasmodium, must traverse tissues and invade a diversity of host cells to ensure successful propagation of their lifecycle. Each lifecycle stage is exquisitely designed for cell movement, tissue targeting and host cell invasion, yet we still do not understand the basic mechanics of how the parasite motor produces force and translates this into powerful movement or cell penetration. Unlike all other eukaryotic cells, the malaria parasites rely on an internal actin-myosin motor, linked through to the outside world through secreted surface adhesins across which it literally glides. Our lab is focused on reconstructing Plasmodium gliding motor function in vitro, its regulation and in a cellular context exploring how the core factors that control motility are distributed. Our work covers the spectrum of scales from single molecule through to whole cell, biochemistry through structural biology and cell biology and, since moving to Imperial, the mysterious world of biophysics. Ultimately our goal is to break apart Plasmodium motility at every level to generate fundamental understanding into parasite biology and identify potential targets to stop the parasite dead in its tracks!

研究领域

Malaria parasites are obligate intracellular parasites that must invade human cells to complete their development. During the blood stages of parasite infection this is undertaken by the merozoite form of the parasite – one of the smallest known eukaryotic cells – that rapidly enters the human erythrocyte in a process that lasts less than 30 seconds. But how does the parasite get into the human cell? In the last few years, insights into the mechanics of parasite invasion have started to be dissected following improvements in our ability to image the events of invasion, capturing and freezing parasites mid way in. Whilst, this has permitted detailed dissection of the molecular architecture of invading parasites and the localization of core molecular components of the invasion machinery by fixed microscopy, we still know very little about the dynamics of live invasion beyond simple black and white wide-field microscopy.

近期论文

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Baum J, Plasmodium MTRAP is essential for vacuole membrane disruption and host cell egress by malaria gametes, Cell Host & Microbe, ISSN: 1934-6069 Bane KS, Lepper S, Kehrer J, Sattler JM, Singer M, Reinig M, Klug D, Heiss K, Baum J, Mueller A-K, Frischknecht Fet al., 2016, The Actin Filament-Binding Protein Coronin Regulates Motility in Plasmodium Sporozoites, PLOS PATHOGENS, Vol: 12, ISSN: 1553-7366 Delves MJ, Straschil U, Ruecker A, Miguel-Blanco C, Marques S, Baum J, Sinden REet al., 2016, Routine in vitro culture of P. falciparum gametocytes to evaluate novel transmission-blocking interventions, NATURE PROTOCOLS, Vol: 11, Pages: 1668-1680, ISSN: 1754-2189 Johnson S, Rahmani R, Drew DR, Williams MJ, Huang JX, Tan YH, Wilkinson M, Tonkin CJ, Beeson JG, Baum J, Smith BJ, Baell Jet al., 2016, Truncated Latrunculins as Actin Inhibitors Targeting Plasmodium falciparum Motility and Host-Cell Invasion, Journal of Medicinal Chemistry, ISSN: 0022-2623 Koch M, Baum J, 2016, The mechanics of malaria parasite invasion of the human erythrocyte - towards a reassessment of the host cell contribution, CELLULAR MICROBIOLOGY, Vol: 18, Pages: 319-329, ISSN: 1462-5814 Olshina MA, Baumann H, Willison KR, Baum Jet al., 2016, Plasmodium actin is incompletely folded by heterologous protein-folding machinery and likely requires the native Plasmodium chaperonin complex to enter a mature functional state, FASEB JOURNAL, Vol: 30, Pages: 405-416, ISSN: 0892-6638 Riglar DT, Whitehead L, Cowman AF, Rogers KL, Baum Jet al., 2016, Localisation-based imaging of malarial antigens during erythrocyte entry reaffirms a role for AMA1 but not MTRAP in invasion, JOURNAL OF CELL SCIENCE, Vol: 129, Pages: 228-242, ISSN: 0021-9533 Tardieux I, Baum J, 2016, Reassessing the mechanics of parasite motility and host-cell invasion, JOURNAL OF CELL BIOLOGY, Vol: 214, Pages: 507-515, ISSN: 0021-9525 Zuccala ES, Satchwell TJ, Angrisano F, Tan YH, Wilson MC, Heesom KJ, Baum Jet al., 2016, Quantitative phospho-proteomics reveals the Plasmodium merozoite triggers pre-invasion host kinase modification of the red cell cytoskeleton, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322 Baum J, Frischknecht F, 2015, Motorizing pathogens., Semin Cell Dev Biol, Vol: 46, Pages: 78-81 Haase S, Zimmermann D, Olshina MA, Wilkinson M, Fisher F, Tan YH, Stewart RJ, Tonkin CJ, Wong W, Kovar DR, Baum Jet al., 2015, Disassembly activity of actin depolymerization factor (ADF) is associated with distinct cellular processes in apicomplexan parasites., Molecular Biology of the Cell, Vol: 26, Pages: 3001-3012, ISSN: 1939-4586 Olshina MA, Angrisano F, Marapana DS, Riglar DT, Bane K, Wong W, Catimel B, Yin M-X, Holmes AB, Frischknecht F, Kovar DR, Baum Jet al., 2015, Plasmodium falciparum coronin organizes arrays of parallel actin filaments potentially guiding directional motility in invasive malaria parasites, MALARIA JOURNAL, Vol: 14, ISSN: 1475-2875 Ortega-Prieto AM, Wai SN, Large EM, Lussignol M, Angrisano F, Blagborough AM, Vizcay-Barrena G, Hughes D, Cooke G, Thursz MR, Fleck R, Baum J, Catanese MT, Dorner Met al., 2015, Microfluidic liver cultures as preclinical tool for the study of hepatitis B and C virus as well as malaria, HEPATOLOGY, Vol: 62, Pages: 1383A-1383A, ISSN: 0270-9139 Wilson DW, Goodman CD, Sleebs BE, Weiss GE, de Jong NWM, Angrisano F, Langer C, Baum J, Crabb BS, Gilson PR, McFadden GI, Beeson JGet al., 2015, Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum, BMC Biology, Vol: 13, ISSN: 1741-7007 Dasgupta S, Auth T, Gov NS, Satchwell TJ, Hanssen E, Zuccala ES, Riglar DT, Toye AM, Betz T, Baum J, Gompper Get al., 2014, Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte, BIOPHYSICAL JOURNAL, Vol: 107, Pages: 43-54, ISSN: 0006-3495 Kan A, Tan Y-H, Angrisano F, Hanssen E, Rogers KL, Whitehead L, Mollard VP, Cozijnsen A, Delves MJ, Crawford S, Sinden RE, McFadden GI, Leckie C, Bailey J, Baum Jet al., 2014, Quantitative analysis of Plasmodium ookinete motion in three dimensions suggests a critical role for cell shape in the biomechanics of malaria parasite gliding motility, CELLULAR MICROBIOLOGY, Vol: 16, Pages: 734-750, ISSN: 1462-5814 Wong W, Bai X-C, Brown A, Fernandez IS, Hanssen E, Condron M, Tan YH, Baum J, Scheres SHWet al., 2014, Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine, ELIFE, Vol: 3, ISSN: 2050-084X Wong W, Webb AI, Olshina MA, Infusini G, Tan YH, Hanssen E, Catimel B, Suarez C, Condron M, Angrisano F, Neb T, Kovar DR, Baum Jet al., 2014, A Mechanism for Actin Filament Severing by Malaria Parasite Actin Depolymerizing Factor 1 via a Low Affinity Binding Interface, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 289, Pages: 4043-4054, ISSN: 0021-9258 Baum J, 2013, A complete molecular understanding of malaria parasite invasion of the human erythrocyte: Are we there yet?, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 107-107, ISSN: 2047-7724 Dahan-Pasternak N, Nasereddin A, Kolevzon N, Pe'er M, Wong W, Shinder V, Turnbull L, Whitchurch CB, Elbaum M, Gilberger TW, Yavin E, Baum J, Dzikowski Ret al., 2013, PfSec13 is an unusual chromatin-associated nucleoporin of Plasmodium falciparum that is essential for parasite proliferation in human erythrocytes, JOURNAL OF CELL SCIENCE, Vol: 126, Pages: 3055-3069, ISSN: 0021-9533