ARDC Research Link Australia

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Orcid icon. 0000-0002-5351-1627

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Research Topics

In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

Publications

Publication

A genetic screen in rodent malaria parasites identifies five new apicoplast putative membrane transporters, one of which is essential in human malaria parasites

Publisher: Hindawi Limited

Date: 09-11-2017

DOI: 10.1111/CMI.12789

Abstract: The malaria-causing parasite, Plasmodium, contains a unique non-photosynthetic plastid known as the apicoplast. The apicoplast is an essential organelle bound by four membranes. Although membrane transporters are attractive drug targets, only two transporters have been characterised in the malaria parasite apicoplast membranes. We selected 27 candidate apicoplast membrane proteins, 20 of which are annotated as putative membrane transporters, and performed a genetic screen in Plasmodium berghei to determine blood stage essentiality and subcellular localisation. Eight apparently essential blood stage genes were identified, three of which were apicoplast-localised: PbANKA_0614600 (DMT2), PbANKA_0401200 (ABCB4), and PbANKA_0505500. Nineteen candidates could be deleted at the blood stage, four of which were apicoplast-localised. Interestingly, three apicoplast-localised candidates lack a canonical apicoplast targeting signal but do contain conserved N-terminal tyrosines with likely roles in targeting. An inducible knockdown of an essential apicoplast putative membrane transporter, PfDMT2, was only viable when supplemented with isopentenyl diphosphate. Knockdown of PfDMT2 resulted in loss of the apicoplast, identifying PfDMT2 as a crucial apicoplast putative membrane transporter and a candidate for therapeutic intervention.

Publication

Development of a Novel CD4+TCR Transgenic Line That Reveals a Dominant Role for CD8+Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria

Publisher: The American Association of Immunologists

Date: 15-12-2017

DOI: 10.4049/JIMMUNOL.1700186

Abstract: We describe an MHC class II (I-Ab)–restricted TCR transgenic mouse line that produces CD4+ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4+ T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human (Plasmodium falciparum) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8+ T cell–mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4+ T cells and the previously described PbT-I CD8+ T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8+ DC (a subset of XCR1+ DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4+ T cell responses. Depletion of CD8+ DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4+ T cell immunity during malaria and provides evidence that CD4+ T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8+ DC.

Publication

A candidate transporter allowing symbiotic dinoflagellates to feed their coral hosts

Publisher: Springer Science and Business Media LLC

Date: 28-01-2023

DOI: 10.1038/S43705-023-00218-8

Abstract: The symbiotic partnership between corals and dinoflagellate algae is crucial to coral reefs. Corals provide their algal symbionts with shelter, carbon dioxide and nitrogen. In exchange, the symbiotic algae supply their animal hosts with fixed carbon in the form of glucose. But how glucose is transferred from the algal symbiont to the animal host is unknown. We reasoned that a transporter resident in the dinoflagellate cell membrane would facilitate outward transfer of glucose to the surrounding host animal tissue. We identified a candidate transporter in the cnidarian symbiont dinoflagellate Breviolum minutum that belongs to the ubiquitous family of facilitative sugar uniporters known as SWEETs ( s ugars w ill e ventually be e xported t ransporters). Previous gene expression analyses had shown that Bm SWEET1 is upregulated when the algae are living symbiotically in a cnidarian host by comparison to the free-living state [1, 2]. We used immunofluorescence microscopy to localise Bm SWEET1 in the dinoflagellate cell membrane. Substrate preference assays in a yeast surrogate transport system showed that Bm SWEET1 transports glucose. Quantitative microscopy showed that symbiotic B. minutum cells have significantly more Bm SWEET1 protein than free-living cells of the same strain, consistent with export during symbiosis but not during the free-living, planktonic phase. Thus, Bm SWEET1 is in the right place, at the right time, and has the right substrate to be the transporter with which symbiotic dinoflagellate algae feed their animal hosts to power coral reefs.

Publication

Glycolipid-peptide vaccination induces liver-resident memory CD8⁺ T cells that protect against rodent malaria

Publisher: American Association for the Advancement of Science (AAAS)

Date: 26-06-2020

DOI: 10.1126/SCIIMMUNOL.AAZ8035

Abstract: Glycolipid-peptide conjugate vaccines protect against rodent malaria by generating large numbers of liver CD8 + T RM cells.

Related Organisations

No related organisations have been discovered for Geoff McFadden.

Related Funding Activities

Grant

Discovery Projects - Grant ID: DP210100639

Start Date: 05-2021

End Date: 12-2024

Amount: $579,000.00

Funder: Australian Research Council

Geoff McFadden

Researcher

Research Topics

Top 5 Research Topics

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

Related Links

Publications

A genetic screen in rodent malaria parasites identifies five new apicoplast putative membrane transporters, one of which is essential in human malaria parasites

Development of a Novel CD4+TCR Transgenic Line That Reveals a Dominant Role for CD8+Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria

A candidate transporter allowing symbiotic dinoflagellates to feed their coral hosts

Glycolipid-peptide vaccination induces liver-resident memory CD8+ T cells that protect against rodent malaria

Related Organisations

Related Funding Activities

Discovery Projects - Grant ID: DP210100639

Discovery Projects - Grant ID: DP1093395

Australian Laureate Fellowships - Grant ID: FL170100008

Discovery Projects - Grant ID: DP160101539

Special Research Initiatives - Grant ID: SR0354678

Discovery Projects - Grant ID: DP130103236

Discovery Projects - Grant ID: DP0664097

Discovery Projects - Grant ID: DP160104980

Federation Fellowships - Grant ID: FF0668705

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100070

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE230100099

Discovery Projects - Grant ID: DP0208165

Special Research Initiatives - Grant ID: SR0354888

Research Networks - Grant ID: RN0460368

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100181

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100011

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE150100004

Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100090

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Glycolipid-peptide vaccination induces liver-resident memory CD8⁺ T cells that protect against rodent malaria