Medical & Health Sciences

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.

Ribosomes are undoubtedly one of the most essential cellular components in life. These macromolecules are responsible for the synthesis of proteins in all living cells. Dr Brigitte Pertschy, Dr Ingrid Rössler and Jutta Hafner at the Institute of Molecular Biosciences at the University of Graz, Austria, have discovered that the safe delivery of essential ribosomal proteins that make up the ribosomes is dependant on ‘private bodyguards’ or ‘chaperones’.

While most people are aware of the health complications associated with diabetes, the impact of maternal diabetes on their children later in life is less understood. A research group at Cincinnati Children’s Hospital Medical Center (Ohio, USA) led by Dr Jane Khoury is working to change this. Their ongoing study, ‘Level and timing of diabetic hyperglycaemia in utero: The transgenerational effect on adult morbidity’ (TEAM study) is driving forward our understanding of the effects of maternal diabetes during pregnancy, to improve healthcare provision for both mothers and their children.

The potential health risks of tattooing are known. However, many of the regulations which govern the practice of tattooing are somewhat relaxed compared to other industries. Dr Christopher Hohl and the Chromatography Section at the State Laboratory Basel-City, Switzerland, work to analyse the composition of tattoo inks and investigate the effects of tattooing to provide the authorities with the evidence needed to improve tattoo safety standards.

Haematopoiesis is the process through which cellular blood components are produced. It starts during embryonic development to ensure the production of blood cells such as erythrocytes (red cells), leukocytes (white cells), and platelets and continues throughout our lives. All blood cells derive from haematopoietic stem cells located in the bone marrow and, unfortunately, blood cancers may occur during this process. Whether blood cells become inefficient or grow excessively, the outcomes are usually devastating. Dr Chen Zhao (University of Iowa) and Dr Qianze Dong (China Medical University) are exploring the cellular mechanisms of haematopoietic stem cells.

In otherwise phenotypical normal females, that is, females with normal ovaries and regular hormone production, Type I Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome results in the absence of the uterus (womb) and the upper two-thirds of the vagina. Type II MRKH syndrome presents with the same utero-vaginal malformation but also further difficulties that can include structural issues within the urological and skeletal systems. Professors Sara Brucker, Olaf Riess, and Oliver Kohlbacher from the University of Tuebingen are elucidating the molecular pathology of the disorder and have developed a surgical intervention to overcome the major life-changing aspects of this condition.

The immune response entails the rapid activation of the immune cells to ensure effective defence from pathogens through the inflammatory pathway, as well as maintain immune homeostasis through the anti-inflammatory pathway. Immune cell activation happens as the result of rapid and severe changes in the expression of the immune-response genes. These depend on regulatory mechanisms controlling the processes of transcription, translation, and modification of these genes to produce functional proteins. Dr Elke Glasmacher, Head of Immune and Cell Biology at Roche, researches the important molecular mechanisms underlying how cells are activated or repressed.