Publications

Strathclyde Minor Groove Binders (S-MGBs) with activity against Acanthamoeba castellanii

McGee Leah MC, Carpinteyro Sanchez Alemao G, Perieteanu Marina, Eskandari Kaveh, Bian Yan, Mackie Logan, Young Louise, Beveridge Rebecca, Suckling Colin J, Roberts Craig W, Scott Fraser J

Journal of Antimicrobial Chemotherapy Vol 79, pp. 2251-2258 (2024)

https://doi.org/10.1093/jac/dkae221

Sodium metabisulfite inhibits acanthamoeba trophozoite growth through thiamine depletion

Mooney Ronnie, Giammarini Elisa, Corbett Erin, Thomson Scott, McKinley Kevin, Sinisterra Sebastian Paula, Rodgers Kiri, O’Donnell Jana, McGinness Charles, Roberts Craig W, Ramaesh Kanna, Henriquez Fiona L

Pathogens Vol 13 (2024)

https://doi.org/10.3390/pathogens13060431

From TgO/GABA-AT, GABA, and T-263 mutant to conception of Toxoplasma

Lykins Joseph, Moschitto Mathew J, Zhou Ying, Filippova Ekaterina V, Le Hoang V, Tomita Tadakimi, Fox Barbara A, Bzik David J, Su Chunlei, Rajagopala Seesandra V, Flores Kristin, Spano Furio, Woods Stuart, Roberts Craig W, Hua Cong, El Bissati Kamal, Wheeler Kelsey M, Dovgin Sarah, Muench Stephen P, McPhillie Martin, Fishwick Colin WG, Anderson Wayne F, Lee Patricia J, Hickman Mark, Weiss Louis M, Dubey Jitender P, Lorenzi Hernan A, Silverman Richard B, McLeod Rima L

iScience Vol 27 (2024)

https://doi.org/10.1016/j.isci.2023.108477

Effects of Biological Sex and Pregnancy on SARS-CoV-2 Pathogenesis and Vaccine Outcomes

Shapiro Janna R, Roberts Craig W, Arcovio Kasandra, Reade Lisa, Klein Sabra L, Dhakal Santosh

Sex and Gender Differences in Infection and Treatments for Infectious Diseases (2023) (2023)

https://doi.org/10.1007/978-3-031-35139-6_4

Sex and Gender Differences in Infection and Treatments for Infectious Diseases

Klein Sabra L, Roberts Craig W

Current Topics in Microbiology and Immunology Current Topics in Microbiology and Immunology, Vol 441 (2023)

https://doi.org/10.1007/978-3-031-35139-6

The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency

Anderluzzi Giulia, Lou Gustavo, Woods Stuart, Schmidt Signe Tandrup, Gallorini Simona, Brazzoli Michela, Johnson Russell, Roberts Craig W, O'Hagan Derek T, Baudner Barbara C, Perrie Yvonne

Journal of Controlled Release Vol 342, pp. 388-399 (2022)

https://doi.org/10.1016/j.jconrel.2021.12.008

More publications

Research Interests

(i) The Shikimate pathway

We have recently demonstrated that the shikimate pathway occurs in Apicomplexan parasites. This pathway is known to also be present in fungi, plants and bacteria, but is notably absent from mammals. This makes it an attractive target for anti-microbial agents. Inhibition of this pathway by n-phosphonomethyl glycine (NPMG), a specific inhibitor of EPSP synthase restricts the growth of T. gondii, P. falciparum and C. parvum in vitro. NPMG was demonstrated to work in synergy with conventional anti-folate drugs such as pyrimethamine and sulphadiazine. The presence of this pathway was further confirmed in 3 members of this phylum (T. gondii, P. vivax and P. falciparum) by identifying and sequencing their chorismate synthase genes (AroC), [Accession U93689, AF451277 and AF008549]. These studies provide definitive evidence that the shikimate pathway occurs in Apicomplexan parasite. Ongoing studies aim to further characterise the shikimate pathway and its potential as a drug target in apicomplexans. In addition we are investigating the evolutionary origin of the shikimate pathway through a phylogentic approach. Results indicate that the shikimate pathway is an ancient eukaryotic innovation that has been selectively lost replaced or retained in different taxa. 

(ii) Fatty acid synthesis

The enzymes of fatty acid biosynthesis are organised differently according to organism. Mammalian enzymes are part of a multi-domain polypeptide which includes acyl carrier protein (ACP), acetyl-CoA-ACP transacylase (ACAT), malonyl-CoA-ACP transacylase (MCAT), ß-ketoacyl-ACP synthase (ß-KAS), ß-ketoacyl-ACP reductase (ß-KAS), ß-hydroxyacyl-ACP dehydrase (ß-HAD) and enoyl-ACP reductase (ENR). This is termed type I fatty acid synthesis. Contrasting with this, the cytosolic bacterial enzymes and platidic enzymes in plants are discrete mono-functional polypeptides. This is termed type II fatty acid synthesis. Differences between these enzymes are the basis of the selectivity of a number of antibiotics including thiolactomycin and triclosan. Recent studies have demonstrated that triclosan is capable of inhibiting the in vitro growth of T. gondii and P. falciparum.

2. Immunological control of toxoplasmosis 

(i) The role of sex and pregnancy associated hormones on the development and maintenance of immunity to T. gondii

We continue to investigate the role of sex and pregnancy associated hormones in influencing the immune system and the development and maintenance of immunity to T. gondii This is of particular interest due to the ability of this parasite to cause congenital disease as levels of many sex hormones, most notably estrogens and progesterone, are vastly increased during pregnancy. The normal physiological role of these changes would appear to be to protect the developing fetus from the mother’s immune response. This is achieved largely through induction of a Th2 biased immune system. However, although this hormonal manipulation of the immune system serves to prevent rejection of the fetus, it also has an important impact on systemic immunity and two important consequences for parasitic infection. Firstly, pregnancy will favor the survival of parasites such as T. gondii that is normally controlled by a type-1 response, Secondly, parasitic infections such as T. gondii that induce a strong type 1 response will adversely affect pregnancy. Both of these scenarios have been demonstrated with the protozoan parasites T. gondi.

(ii) Vaccine Design for T. gondii

The ability a natural infection in humans with T. gondii to induce a level of immunity capable of preventing congenital transmission demonstrates the feasibility of a vaccine. We have developed a number of models of disease, including a congenital model that facilitates the evaluation of vaccine constructs. Current research aims to identify vaccine candidates using DNA vaccine technology.

(iii) Control of parasite multiplication, immunopathology and immune privilege

Immunological control of Toxoplasma gondii is complex and involves almost all facets of the immune response. Understanding the pathogenesis of this disease is key to the development of vaccines and immuno -therapeuatic agents. Current research is investigating the role of the immune response in controlling parasite multiplication and in causing immunopathology especially at immune privileged sites such as the eye and brain. Results indicate that successful resolution of disease is a delicate balance of proinflammatory mechanisms and anti-inflammatory mechanisms. Furthermore, T. gondii would appear to disrupt aspects of immune privilege, such as the low levels of MHC class I molecules in the retina while accentuating other aspects such the constitutive expression of TGF-β.

3. Antimicrobial Agents for treatment of Acanthamoeba infection and improved contact lens solutions

Acanthamoeba (species) are an important cause of microbial keratitis that may cause severe ocular inflammation and visual loss. The first cases were recognised in 1973, but the disease remained very rare until the 1980s when an increase in incidence mainly associated with contact lens wear was reported. Acanthamoeba are ubiquitous free-living protozoa, which normally exist in water. Contact lens rinsing and soaking solutions prepared with non-sterile water is the usual source of infection. Medical cure is difficult and relies on early diagnosis and treatment with multiple anti-microbial agents. A corneal graft may be required due to the extensive destruction caused by the parasite. Furthermore, the ability of the trophozoite to from cysts stages that are resistant to chemotherapy reduces the chances of a medical cure. Sadly, in many cases the donor cornea is subject to infection as the disease reactivates. Acanthamoeba keratitis has now been recognised world-wide and there is no evidence to suggest that the incidence of this disease is declining. 

New, more effective therapeutic strategies capable of completely eliminating infection are required. We have recently developed a 96 well plate colourimetric assay to measure the efficacy of antimicrobials against Acanthamoebaand current research concentrates on target identification and validation for new antimicrobials. 

In addition contact lens solutions currently available do not reliably kill Acanthamoeba. Rcently there have been a number of outbreaks of infection that have led to the recall of certain particularly dangerous contact lens solutions. In recognition of the growing importance of Acanthamoeba infection in contact lens wearers, the FDA convened a workshop on ‘Microbiological Testing of Contact Lens Care Products' (January 23, 2009), with many stakeholders in the industry. As a result of this, ISO 14729, the international standard used to test the antimicrobial ability of contact lens solutions, is currently being revised to include Acanthamoeba as a test pathogen. Further work concentrates on developing new more effective contact lens solutions.

Opportunities for Post Graduate Research

Projects are available (subject to funding) in the above areas for students wishing to study towards a Ph.D. Applications should be submitted through the Graduate School.

Publications

Books Edited

1. Sex Hormones and Immunity to Infection (2009) ed. Klein, S., & ROBERTS, C.W. Springer. (ISBN 978-3-642-02154-1) 

online version: 

http://www.springerlink.com/content/978-3-642-02154-1

hard copy:

http://www.springer.com/biomed/immunology/book/978-3-642-02154-1

Professional Activities

65th Annual Meeting American Society of Tropical Medicine and Hygiene

Keynote/plenary speaker

10/2016

BioMed Central (Publisher)

Peer reviewer

2016

Medical Research Council (External organisation)

Member

2016

PLoS ONE (Journal)

Peer reviewer

2016

FASEB Journal (Journal)

Peer reviewer

2016

Applied and Environmental Microbiology (Journal)

Peer reviewer

2016

More professional activities

Projects

NISV - Non Ionic Surfactant Vesicles

Roberts, Craig (Principal Investigator) Perrie, Yvonne (Co-investigator) Woods, Stuart (Research Co-investigator)

01-Dec-2022 - 27-Sep-2024

NISVs as a drug delivery and targeting system for antimicrobials

Woods, Stuart (Research Co-investigator) Roberts, Craig (Co-investigator) Williamson, Diane (Co-investigator) D'Elia, Riccardo (Principal Investigator) Preston, Jane (Research Co-investigator) Dye, John (Co-investigator) Hu, Weigang (Co-investigator)

FMS costing ID 11620

01-Feb-2022

New Application of a DNA-nanorod Platform for Vaccine Development

Yu, Jun (Principal Investigator) Chen, Yu (Co-investigator) Roberts, Craig (Co-investigator)

A Novel DNA-nanorod platform for diverse Chemeric viral Vaccine Development Stream 1 - Scientific and Technical Feasibility

01-May-2017 - 30-Apr-2018

Leveraging Pharmaceutical Sciences and Structural Biology Training to develop 21st Century Vaccines PHA-ST-TRAIN-VAC (H2020 MCSA EID) | Lou Ramirez, Gustavo

Perrie, Yvonne (Principal Investigator) Roberts, Craig (Co-investigator) Lou Ramirez, Gustavo (Research Co-investigator)

01-Jan-2017 - 28-Feb-2020

Understanding and preventing congenital toxoplasmosis

Roberts, Craig (Principal Investigator)

17-Aug-2015 - 16-Aug-2016

BB/J013854/1 BBSRC DPT Studentships (with Glasgow University) | Hargrave, Kerrie

Roberts, Craig (Principal Investigator) Wiese, Martin (Co-investigator) Hargrave, Kerrie (Research Co-investigator)

01-Oct-2014 - 29-Mar-2019

More projects