Research suggests new therapeutic targets for broad-spectrum antiviral drugs

As an analogy, when the axon is scaled up to be the arm in a human body, you can think of the axon length in relation to the neuron's cell body as the equivalent distance from Nottingham to Paris. This significant length poses a logistical challenge for the neuron. For proteins to be expressed at the axon terminal, which is distant from the cell body, there's a requirement for translation regulation. In other words, there is a need for descentralized gene expression. Here, small non-coding RNAs play a pivotal role. Our work on microRNAs has shown their importance in spatial-temporal control of gene expression. This research aligns with the current interest in RNA biology and offers potential avenues for drug discovery, especially given the advances in RNA technologies post-covid.

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.

Traditional cancer treatments have been largely unfocused in that they indiscriminately kill dividing cells, cancer or otherwise, which often leads to significant toxic side effects in patients. Targeted therapies on the other hand, try to inhibit one or more abnormal proteins that are found in proliferating cancer cells resulting in programmed cell death. One or more mutations in the p53 gene are found in at least 50% of all human cancers. These mutations begin a sequence of events that leads to loss of control of cell growth and proliferation. Due to its central importance in many human cancers, drugs that restore function to mutated p53 proteins have been described as one of the three holy grails of cancer research. Targeting specific abnormal proteins found only in cancer cells could be expected to be associated with less toxicity in normal healthy cells.

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.

The study by Williams was looking for variations in hemoglobin, the oxygen-binding protein found in red blood cells. There are disorders which lead to abnormalities in hemoglobin, which can cause serious illness or even death. Identifying these variants would lead to a better prognosis for people with such abnormalities, and the study found a variant by having the ability to differentiate between leucine and isoleucine. Methylmalonic acidemia (MMA) and propionic acidemia (PA) are metabolic disorders resulting from an inability to break down isoleucine, valine, methionine, and threonine (which are also amino acids), odd-chain fatty acids, as well as cholesterol. These are rare diseases which are known as “inborn errors of metabolism” (IEM). The restriction of certain foods and the use of medical foods can form part of the treatment for IEM disorders. Leucine is added to a lot of these medical foods, and is hence selected for patients with MMA and PA. As patients with MMA and PA cannot break down isoleucine and valine, foods containing these amino acids should be avoided. However, it was previously reported that avoiding such amino acids can lead to an imbalance in the amounts of branched chain amino acids in the blood. More specifically, the ratio of leucine to isoleucine/valine was found to be increased. This could have dire consequences, potentially disrupting the synthesis of neurotransmitters due to impaired amino acid transport into the brain. In this case, it would be pivotal to distinguish between leucine and isoleucine, as the balance between these two amino acids needs to be restored to avoid potential damage.