National Postdoc Appreciation Week - University of Dundee

Group A Streptococcus (Strep A) is a bacterial pathogen commonly found in the skin and in the throat. Strep A induces mild infections like pharyngitis, also known as strep throat, impetigo, and scarlet fever. However, the pathogen in some cases may lead to invasive Strep A infections such as Necrotising fasciitis (flesh-eating disease) and autoimmune diseases like acute rheumatic fever and rheumatic heart disease. Frequent episodes of strep throat which is untreated or undertreated can sometimes lead to acute rheumatic fever. Multiple episodes of acute rheumatic fever have been shown to increase damage to the heart muscles resulting in rheumatic heart disease (RHD). More than half a million people have been affected by RHD annually and the data shows that children aged 5-14 years are the most likely affected by the invasive Strep A infection. Even though antibiotics, can cure strep throat there have been few studies that showed antibiotic resistance to Strep A strains. So an effective way to combat the disease would be to develop new vaccines that could drastically prevent the need to use antibiotics, given strep throat is a major contributor to global antibiotic use. One of the challenges to developing a universal Strep A vaccine is to overcome the pathogen’s extensive antigenic variation and genomic diversity found in Strep A serotypes. At the forefront of addressing this challenge, here, at the University of Dundee, we use Group A Carbohydrate (GAC), a major component present in the cell wall of the bacteria as our immunogen. GAC is highly conserved in all the Strep A serotypes found so far. Our research uses a smarter way to produce glycoconjugate vaccines called the protein glycan coupling technology method (PGCT). Implementing the PGCT method allows us to develop GAC as an immunogen by conjugating them with the potential carrier proteins from the same pathogen. The developed glycoconjugate vaccine candidates have been tested vigorously in the pre-clinical trials using mice and rabbit models. We demonstrated that the IgG antibodies from the animals vaccinated with the glycoconjugate were highly immunogenic and were able to kill the Strep A strains.
Join me at the Ninewells Hospital on the 18th of September where I explore the ground-breaking research on addressing the need for Strep A vaccines and discuss the possibilities of developing glycoconjugate vaccine candidates and their immunogenicity against Strep A. This presentation will not only shed light on the development and testing of the vaccines but also outline the requirements for the universal life-saving Strep A vaccine to market.

Glioblastoma multiforme (GBM) accounts for over half of primary brain malignancies and represents a major health burden due to lack of effective treatment options owing to it's diffuse nature. The tumour microenvironment (TME) of GBM is considered to be immunosuppressive and contains many tumour associated macrophages (TAMs). As NRF2 has a key role in regulating immunity, we hypothesise that GBM cells communicate with TAMs to increase NRF2 signalling and drive immunosuppression and disease progression.

Chemotherapy induced peripheral neuropathy (CIPN) is a prevalent (30%-68%) and serious side effect of neurotoxic chemotherapy potentially impacting patient survival, and adversely affecting quality of life (1,2). It is characterised by symptoms such as tingling, numbness, and pain in the hands/feet which can be acute or chronic. Patients may be cured of their cancer, but chronic CIPN is more likely to be persistent (1). Although CIPN is widely acknowledged as a serious clinical problem, there are still NO THERAPEUTIC OPTIONS available to prevent CIPN (3). This systematic review was prospectively registered on PROSPERO, ID: CRD42023429136. BT, AC and MG screened the titles and abstracts of the identified records on Covidence, and any conflicts were resolved by LC. There were 206 reports with 104 published studies and data from 102 ongoing clinical trials and unpublished studies. Within the published studies, there were 23 studies with data from pharmacological studies and 81 studies with results from non-pharmacological therapies. Pharmacological therapies included duloxetine, acetyl-L-carnitine, Amitriptyline, glutamine while non-pharmacological approaches included compression, cryotherapy, frozen gloves, exercise, and vitamins. There were 12 different clinical trial registries from across the world that contributed to the data (n=102).In 2020, ASCO guidelines (3) discouraged use of acetyl L carnitine and NO RECOMMENDATIONS were made for all the agents currently being studied. Additionally, the reporting of results and data regarding causes for early termination of clinical trials can inform development and planning of future studies to prevent CIPN.