Medical & Health Sciences

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.

UK Biobank is a large-scale biomedical database and research resource containing genetic, lifestyle and health information from half a million UK participants. The database, which is regularly augmented with additional data, is globally accessible to approved researchers and scientists undertaking vital research into the most common and life-threatening diseases. UK Biobank’s research resource is a major contributor to the advancement of modern medicine and treatment and has enabled several scientific discoveries that improve human health. In this exclusive interview, we speak with Professor Sir Rory Collins FMedSci FRS, Principal Investigator and Chief Executive of UK Biobank, to hear about the achievements to date and the ambitious and unique potential of this exciting project.

The effectiveness of cancer treatments could be hugely improved by a greater understanding of the cancer genome. This is the focus of the work of Dr John Paul Y.C. Shen, MD, of the University of Texas MD Anderson Cancer Center, who is creating comprehensive molecular ‘maps’ of cancer cells and their interactions. Understanding cancer at a molecular level is the first step towards Dr Shen’s very real hope of bringing personalised cancer treatments into the clinic.

The discovery of DNA has been one of the most important findings of the last century, yet there is still much more to uncover about the ‘additional chemical layer’ brought about by the chemical modification of amino acids and nucleotide bases. A large collaboration of researchers at institutions across Germany, known as SFB 1309, is led by Professor Thomas Carell at the Ludwig-Maximilians University in Munich. A key focus of SFB 1309 is to elucidate the details of the second layer of information beyond the sequence layer of biochemical molecules called Watson-Crick bases within our DNA.

Head and neck squamous cell carcinoma (HNSCC) constitutes around 90% of all head and neck cancers. Millions of individuals are diagnosed across the globe every year, very often too late and with poor prognosis. Among other factors, alcohol consumption and smoking increase the risk to develop HNSCC. Dr Muy-Teck Teh, from Queen Mary University of London, is driving forward our understanding of the factors leading to cancer, leading the development of novel less invasive detection methods, and progressing better therapeutic options.

Nitric oxide is an ‘A-list’ celebrity amongst chemical compounds. Proclaimed ‘molecule of the year’ in 1992 by the American Association for the Advancement of Science, its physiological importance, discovered in 1985, was recognised in 1998 by the award of a Nobel prize to some of the researchers who had discovered its vital role in regulating blood vessels and blood pressure. Here we look at the pre-eminent work of Dr Alan N. Schechter at the National Institutes of Health in Bethesda, Maryland, USA, that is continuing to keep nitric oxide at the front and centre of groundbreaking biological research.

Differences in the prevalence and survival of male and female cancer patients have long been acknowledged but not well understood. Dr Josh Rubin (Departments of Paediatrics and Neuroscience at Washington University) and his collaborators have been the first to identify sex-specific differences in malignant transformation. This evidence will help to optimise sex-specific approaches to cancer treatment and contribute to the improvement of the outcomes and survival of cancer patients.

The eye movement disorders strabismus (characterised by eye misalignment) and nystagmus (characterised by involuntary oscillation of the eyes) together affect up to 5% of the population and have a detrimental impact on vision. These disorders also impact on facial appearance and social interaction, which may, in turn, lead to psychological difficulties. Dr Mary Whitman, at the Boston Children’s Hospital, USA, is working to understand the genetic causes and neurological mechanisms underlying eye movement disorders to improve treatment and, ultimately, prevent their onset.

Professor David Magnuson, at the University of Louisville, Kentucky, describes himself as ‘a CPG guy’ and occasionally, more informally as ‘a rat guy!’ His work on the function of the central pattern generator (CPG) in the rat spinal cord following spinal cord injury, has produced both surprising and thought-provoking results. This research may ultimately challenge the established clinical beliefs and practices around the ways to best rehabilitate human patients with severe spinal cord injury.

Cells possess the ability to interact with one another through complex signalling pathways. Different signals regulate how cells differentiate, undergoing modifications that ultimately allow them to adopt different cell fates and perform specific functions. The laboratory of Professor Kim Dale from the University of Dundee, Scotland, has made seminal contributions to our understanding of how the Notch signalling pathway controls the formation of tissues and organs in the earliest stages of development. Their important research has unveiled new insights into the molecular basis of Notch signalling in the context of normal development which will further our understanding of the molecular basis of developmental disorders and a multitude of diseases correlated with aberrant Notch signalling.

Pancreatic ductal adenocarcinoma (PDA) is an aggressive type of cancer. It is relatively common and is one of the leading causes of cancer mortality. Unfortunately, it is often detected only in the late stage of the disease and fails to respond to pre-surgical approaches, such as chemotherapy or radiotherapy, that are needed to shrink the tumour mass before surgical removal. Dr Scott Gerber at the University of Rochester Medical Center, USA, is working with colleagues to develop a novel combined therapy to overcome this issue and increase the survival of PDA patients.

Sorghum is a staple crop in many regions of the world. As such, this versatile plant has been selectively bred into a number of cultivars, including sweet varieties predominantly used for forage, silage, sweet syrup and bioenergy production. Dr Elizabeth A. Cooper and her team at the University of North Carolina at Charlotte generated a full reference genome for the sweet sorghum cultivar ‘Rio’ with the aim of understanding the genetics underlying the differences between grain and sweet cultivars. Their research could provide a vital tool for biologists and breeders to improve sweet sorghum lineages.

Prader-Willi Syndrome is a rare genetic neurodevelopmental disorder that gives rise to a vast array of symptoms which affect the individual from birth. There is currently no cure for Prader-Willi Syndrome. Professor Gordon Carmichael and his team from the Department of Genetics and Genome Sciences at the University of Connecticut Health Centre, USA, believe it is crucial to understand the affected chromosome 15 region to unravel the pathogenesis of Prader-Willi Syndrome and his team are making significant strides towards achieving this goal.

For life on Earth to grow, its genetic material must be copied and reproduced in a process known as DNA replication. Professor Michael O’Donnell, head of the Rockefeller University’s DNA replication laboratory, has devoted his over 30-year career to the study of the protein complex that is responsible for just that – the replisome. Recently, Professor O’Donnell and his team uncovered exciting insights into the function of this remarkable piece of molecular machinery.

The UNAIDS estimates that 38 million people currently live with human immunodeficiency virus (HIV) infection. Combination antiretroviral treatment has had great success in saving lives but is also associated with numerous medical and public health challenges. Vaccination remains the best and most cost-effective option for controlling HIV infection across the world. Professor Tomáš Hanke jointly from the University of Oxford, UK, and Kumamoto University, Japan, designs vaccines and coordinates clinical programmes testing the most advanced vaccine candidates developed by his team in the UK, Europe, USA and Africa.