Biology

While antibiotics have transformed modern medicine, helped to extend life expectancy in the UK by as much as 20 years and saved millions of lives around the world, the rapid rise of resistance to these drugs presents an imminent global health disaster if not adequately managed in the very near future. In this exclusive interview, we speak with Professor Colin Garner, founder and Chief Executive of Antibiotic Research UK, the world’s first charity focussing on bacterial antibiotic resistance, to hear about their vital efforts targeted at overcoming the challenge of antibiotic resistance.

Bacteria are found everywhere – in humans, animals and the environment – and are best known for being able to cause painful and even fatal infections. It may come as surprise, therefore, to learn that bacteria can also have useful applications. The lifetime work of Dr Bert Lampson at East Tennessee State University in the USA has focussed on the dangers and applications of bacteria. Over his career, Dr Lampson has discovered new mechanisms of antibiotic resistance, novel antibiotics, and bacterial proteins, with important applications for science and healthcare.

The availability of skilled health practitioners is fundamental to the health of a nation. Unfortunately, many countries experience shortages of healthcare professionals. Shortages typically result when too few choose to enter the health professions and when too many exit the health professions, whether to pursue an alternate career or to retire. Dr Sarah Hewko, based at the University of Prince Edward Island, is conducting valuable research into the reasons why health professionals retire earlier than planned.

Rheumatoid arthritis (RA) is a long-term, systematic disease that causes pain, swelling and stiffness in the joints. Professor Hani El-Gabalawy and his research team from the University of Manitoba in Canada are finding ways of better identifying those at risk for future RA as a prelude to developing and testing prevention strategies. Since other autoimmune diseases are known to have similar preclinical phases, prevention strategies that can effectively lower the risk of developing RA can potentially be adapted and applied to a broad range of similar disorders.

Being overweight is a well-recognised risk factor for the development of chronic diseases such as diabetes, heart diseases, and certain types of cancer. As such, obesity represents a significant public health issue worldwide. It is the leading cause of death in the USA, notably in Arkansas, where Dr Jamie I. Baum, at the Department of Food Science at the University of Arkansas, is exploring, with her colleagues, the relationship between dietary protein intake and its impact on body composition and metabolism to develop efficient nutritional guidelines to prevent and treat obesity.

Ultraviolet radiation (UVR) from sunlight has been identified as a leading risk factor for the development of melanoma. Despite numerous research studies, the molecular mechanisms underlying the link between UVR and melanoma remain still poorly understood. Dr Chengyu Liang, from The Wistar Institute in Philadelphia and her collaborators from the University of Southern California have identified the function of the UV irradiation resistance associated gene (UVRAG). Their studies show that inactivation of UVRAG affects the ability of the cell to repair UVR-induced damage mechanisms. The researchers also provide compelling in vivo validation of a novel prognostic and predictive biomarker in melanoma.

Immune system cells express a number of receptors that bind to sugar ligands. This binding initiates the activation of T-cell lymphocytes and natural killer cells. Dr J. Kenneth Hoober, Dr Laura L. Eggink and the team at Susavion have designed peptides that bind to different receptors on immune cells. The peptides effectively extend the lives of mice with glioblastoma and ovarian cancer, and prevent the replication of viruses in the presence of non-neutralising antibodies. The mechanism of action of their peptides could inspire the development of effective treatments for Covid-19 and other viral infections.

The human heart is a muscle, and like all types of muscles, it can be injured. In humans, heart muscle is not able to regenerate after injury, and this can lead to heart disease which develops over time, eventually leading to an untimely death. A team of researchers, Doctor Claudine Bruck (Prolifagen), Professor Edward Morrisey (Department of Medicine and Cell and Developmental Biology) and Professor Jason Burdick (Department of Bioengineering) at the University of Pennsylvania, have collaborated to develop a novel therapy to regenerate damaged heart muscle.

Prolonged exposure to nitrate from contaminated water affects the transport of oxygen in blood. Nitrate can react with haemoglobin, oxidising it into methaemoglobin, which is unable to carry oxygen. High methaemoglobin levels among infants result in a medical condition known as methaemoglobinemia or blue baby syndrome. Dr Mina Sadeq and her team from the National Institute of Hygiene in Morocco, conducted two studies to investigate the combined effects of nitrate and bacteria on the development of methaemoglobinaemia in infants and young children.

Liquid biopsies have recently gained attention as sources of non-invasive diagnostic cancer biomarkers. Traditional biofluid sampling methods, however, are onerous and time-consuming and present many limitations including poor sensitivity for biomarkers in low concentrations. Dr Anton Iliuk and his team at Tymora Analytical Operations, West Lafayette, USA, have developed a way to isolate extracellular vesicles from plasma, urine and other biofluids. They now aim to grow their network of collaborators to use their platform for the discovery of protein biomarkers from several cancers, neurodegenerative diseases, and other conditions.

Applying mathematics to biology can help reveal the elusive details of life. Professor Wilfred D. Stein and his colleagues from the Hebrew University of Jerusalem and institutes worldwide have used quantitative tools to tackle topics ranging from cancer treatment to drug-resistant malaria, and lately, the evolution of the human genome. His extensive and broad work has supported scientists in many different areas of biomedicine and will leave a lasting impact on life science.

Sepsis is a serious medical condition that manifests with a dysregulated immune response to an infection in the bloodstream, and is a major cause of morbidity and mortality worldwide. Many non-infectious conditions can lead to a state of hyper-inflammation known as the systemic inflammatory response syndrome (SIRS), which clinically can look very similar to sepsis. A lack of analytical tools that allow for the early detection of sepsis makes discrimination between sepsis and SIRS a very complex but critical diagnostic task. Dr Richard B. Brandon, Dr Thomas D. Yager and their colleagues at Immunexpress have developed a molecular diagnostic platform capable of detecting genetic biomarkers diagnostic for sepsis in about an hour. Early sepsis diagnosis can potentially lead to better patient management, more efficient use of resources, and a more sensible approach to the use of antibiotics.

Healthcare systems around the world are under increasing pressure as a result of depleting resources accompanied by rising demands. Dr Johannes Bircher’s reflections on the inherent failings of modern healthcare systems have coalesced into an important proposal for a new concept of health, known as the Meikirch model. Here, we look at the potential of the Meikirch model to drive forward a critical paradigm shift in healthcare delivery.

Investigating the role of an immune system protein, GANP, and its coding gene, ganp, Dr Yasuhiro Sakai and Dr Kazuhiko Kuwahara (Fujita Health University School of Medicine) have unveiled a potential role for this important protein in tumourigenesis. The scientists apply a multidisciplinary approach to identify potential therapeutic solutions to aid cancer prognosis, a collaboration that occurs in the emerging field of immunopathology. The researchers focus on the differential levels of GANP which appear to correlate with breast cancers (low GANP) and with lymphocytic cancers (high GANP).

The rise of pandemic-causing viruses is a worrying development arising as a by-product of our hugely connected world, and scientists must forge new paths to tackle these diseases. With researchers like Dr Babita Agrawal from the University of Alberta at the helm, we can hope to enter a new era of preventatives and therapeutics to help us fight disease. Dr Agrawal and her team are investigating novel vaccines and immunotherapeutics for influenza, Hepatitis C, tuberculosis, and even cancer.

Ubiquitin is a polypeptide that is tagged on to various proteins to signal a range of biological processes. The alteration of the ubiquitin system plays a pivotal role in the pathogenesis of diseases including autoimmune disorders and cancer. The process of ubiquitinylation involves a cascade of enzymes, E1, the activating enzyme, E2 (conjugating enzymes) and E3 (ligases). Characterisation of the ubiquitinylation process of key proteins that impact stems cells, immune cells, and cancers is vital to identify therapeutic targets which may influence the progression of autoimmune conditions and cancers. The ubiquitin system is compromised in the majority of cancers and is the focus of research by Dr Yi Sheng of York University, Canada.

Multidrug resistance is one of the main culprits underlying the failure of chemotherapy as a cancer treatment. Whilst many therapies are initially effective, a considerable proportion of patients eventually incur a poor prognosis and recurrence of malignant spread due to developing drug resistance at a later stage. Dr Rock J. Mancini, from Washington State University, has devised an approach that exploits proteins over-expressed in drug-resistant cancers to convert inactive prodrug substrates into active drugs that initiate an immune response targeted at cancer cells.