Naturally occurring peptide can reverse drug resistance in melanoma

I am going to be talking about new columns based on ionic liquids. An ionic liquid is a liquid in which all the components are ions, like salt (sodium chloride), only, instead of being a solid, it is a liquid. These things have very high polarity and can be developed with extremely high thermal stabilities. They are highly useful as GC stationary phases, which I will be talking about. They are really useful as headspace solvents for the analysis of environmental and biological samples. We use it to analyze water and all sorts of materials. That is the thrust of what I will be talking about, new ionic liquids that are highly polar, highly stable and can be used for unusual analyses that ordinary stationary phases and ordinary techniques have difficulty with.

Certainly. We're keenly exploring extracellular vesicles as mediums for cells to communicate. These cell made vesicles often carry microRNAs and other non-coding RNAs, presenting a unique avenue to understand how neurons modulate their environment, which is especially interesting in neurological conditions. We are exploring extracellular vesicles as these tools with which cells can communicate and transfer gene expression patterns. And we're looking at, for example, how early life brain tumours such as medulloblastoma can impact neuron development and activity and how this can affect later life pain processing and neurological conditions. This has been possible via funding from the Medical Research Foundation, which supported a big collaboration between the labs of Gareth Hathway, Beth Coyle, Vicky James, Anna Grabowska and myself in Nottingham.

We are now testing the drug in patients with earlier-stage pancreatic cancer, prescribing it while their tumors are still operable and before their cancer spreads.

S. aureus is a Gram-positive and cocci-shaped bacterium, meaning that it appears purple with ‘Gram stain’, and these bacterial are seen as clusters of small, spherical cells. S. aureus is a part of the human microbiome – mostly being found on the surface of the skin and all mucous membranes (e.g. eyes, mouth and ears). They are opportunistic bacteria, meaning that if a break in the skin occurs, or if the host becomes immunodeficient in some way, S. aureus can eventually cause an infection. When S. aureus does infect a human host, it may result in a variety of different diseases, but very commonly it causes recurrent soft tissue and skin infections. These infections have become more prevalent in recent years, mainly as nosocomial forms, as methicillin-resistant strains of S. aureus (MRSA) have evolved in hospitals across the western world. In humans, protein A (once it is released into the extra-cellular environment) can bind with the ‘Fc’ fragment of immunoglobulin G (IgG) and has been observed to be antiphagocytic in vitro - which is consistent with its IgG binding abilities, as binding to IgG can interfere with bacterial attachment by the antibody. This means that it can prevent itself from being destroyed by certain elements of the human immune system (as was also similarly observed in the guinea pig experiment from 2013). S. aureus infections, such as endocarditis, are usually treated with a strong course of antibiotics. Protein A can therefore function slightly differently in different species, but always has the same goal: it interferes with the host’s B-cells within their immune system to prevent S. aureus from being phagocytosed and destroyed. This is an ideal adaptation, and when coupled with the known propensity of S. aureus to be more easily transmitted than other coagulase-positive bacteria, it indicates faster and more widespread bacterial transmission.

There has been a regulatory drive to reduce animal testing for some time, including through frameworks such as the European Union’s REACH directive. More recently, we have seen this strengthened with roadmaps to phase out animal testing for chemical safety. In silico and in vitro methods are likely to be central to that transition. These tools can provide efficient, human-relevant, and multiscale evidence. One could imagine an approach similar to the carcinogenicity weight-of-evidence approach, in which in vitro and in silico data are gathered to justify reduced or no animal testing at specific points in the approval process. Regulatory acceptance remains challenging because standards vary around the world. For AI, there are also questions about model approval, model updates, benchmarking, and version control. It will be very interesting to see how regulators test and define these pathways.