Celebrating Research: 110th Anniversary
In recent months, members have been nominating small molecules of significance for Lizzie to draw for printing onto transparent vinyl to bejewel windows in offices and labs.
Each group has nominated important molecules involved in their area of research for installation on the windows in their labs and offices.
Molecules are printed and carefully cut out ready for installation on their windows
This synthetic molecule was developed in the 1950s initially as an antimalarial drug and is used in the treatment of a wide variety of conditions such as systemic lupus erythematosus and rheumatoid arthritis. In 2015, scientists from the department showed that hydroxychloroquine also inhibits the pace making current I f and noted additional effects on the L type calcium channels and delayed rectifier potassium channels, indicating multi ion channel block in cardiac cells.
Noradrenaline (also known as norepinephrine) is made in our body and functions in our brain and body as both a hormone and neurotransmitter to mobilise us into action. Release of noradrenaline is lowest while we sleep and highest during stressful situations. It increases focus together with elevating heart rate and blood pressure, and release of glucose into our blood ready for our skeletal muscles all involved in the ‘fight or flight’ response to danger.
Acetylcholine was the first chemical neurotransmitter discovered. It binds to specific cell membrane receptor proteins, stimulating action. Among other actions it controls muscle contraction, and in the cardiovascular system stimulates small cells lining the inner surface of blood vessels This activates signalling mechanisms to keep vessels open and prevent blood pressure from getting too high.
The synthetic IMP-1575 molecule binds to a protein in our cells called membrane bound acetyltransferase (MBOAT). The MBOATs are a family of proteins involved in many biological
processes including growth, development and appetite. A drug to inhibit these proteins brings possibilities for treatment in cancer and obesity.
IMP-1700 is a synthetic molecule has been found to prevent DNA repair in bacteria. While antibiotic resistance is increasing in the environment, IMP-1700 gives the possibility for using in combination with drugs that could damage DNA, and so making bacteria more sensitive.
This synthetic drug was derived from a chemical, myriocin, found in a fungus, Isaria sinclarii, and in traditional Chinese medicine for ‘eternal youth’. Fingolimod is an FDA approved drug to treat multiple sclerosis. Through investigating its cardiac protective effects and action mechanisms, Lei Group has deve loped a novel class of small molecular drug agents for treating hypertrophic heart disease and ventricular arrhythmias.
The image presents the complex between the neurotrophin NGF and its high affinity receptor TrkA , particularly the immunoglobulin like domain 5 (d5), which is necessary and sufficient for NGF binding. The NGF TrkA receptor activation, among other things, controls the activity of nerve cells involved in cognitive processes such as learning and memory. Alteration of neurotrophin signalling in specific neurons contributes to neurological conditions.
Lucerastat and Miglustat have the same molecular composition, but differ in subtle changes of shape. This small molecule is being investigated for tre at ment of a rare genetic disorder, Fabry disease. This disorder comes from disruption in how the body metabolises glycosphingolipid (fat) within structures call ed lysosomes found inside our cells. The tiny difference in the structure of Lucerastat changes the enzymes it interacts with and therefore has fewer side effects than Miglustat.
Miglustat is a small molecule that was developed by Oxford GlycoSciences and then Actelion and used to treat two lysosomal diseases called Gaucher disease and Niemann Pick disease type C (NPC). The molecule helps slow down the synthesis of glucosylceramide and its derivatives which in patients with Gauch er and NPC can build up and become harmful to the body. Miglustat is a substrate reduction therapy drug approved for clinical use.
Ezutromid MoA probe C17H8F3N3O
This molecule is based on ezutromid, a drug candidate for Duchenne muscular dystrophy developed in partnership between Oxford University and Summit Therapeutics. The probe allows the elucidation of the mechanism of action of ezutromid and has opened the door to the development of next generation drugs for the treatment of Duchenne. This molecule interacts with the aryl hydrocarbon receptor.
This small molecule is made in our body where it functions as a neurotransmitter. Its role is complex and multifaceted in processes in the brain including mood, cognition, reward, learning, memory as well as processes involved in vomiting and vasoconstriction. Serotonin is primarily found in our guts whe re it regulates movement in our intestines and may relate to those ‘gut feelings’.
Levetiracetam is an unusual drug used in treating several types of epilepsy. Although very effective, levetiracetam works in a d ifferent way to other anti seizure drugs although not properly understood. “My work focusses on investigating the novel mechanisms by which levetiracetam suppresses seizures and exploring whether this dr ug could help with other diseases.”
Ryanodine is a potent and deadly chemical which forms a natural insecticide found in the South American plant Ryania speciosa . When introduced into animals, ryanodine will bind to calcium release channels which are found in high numbers in cells in the h eart, skeletal muscle and brain. The calcium release channels are named ‘ryanodine receptors’ because ryanodine binds only to these channels, binding extremely ti ghtly and destroying the calcium releasing properties of these channels that are essential for life. Ryanodine has been a crucial tool that allows ryanodine receptor calcium release channels to be purified so the function and structure of the channel s can be studied. Our group has focussed primarily on ryanodine receptor channels in the heart, aiming to understand how channel opening is controlled normally and what changes in di seases such as heart failure and inherited lethal arrhythmic conditions caused by mutations to the ryanodine receptor.”
Anthracene-9-carboxylic acid C15H10O2
This molecule is used in the lab to study the function of ion channels. Ion channels are microscopic pores found on virtually all cell membranes where they allow charged ions, such as chloride, to move in an out of the cell. The resulting changes in voltage control a vast array of bi ological functions, including heart beat and cognition. A9C blocks chloride ion channels like a cork in a bottle. Thus A9C can be used to examine the consequence s o f “inactivating” chloride channels in cells and tissues to learn about the fundamental functions these channels play in different organs.
Originally found in the bacterium Streptomyces peucetius, this toxin is used in chemotherapy. Doxorubicin slows growth of cells through blocking an enzyme called topoisomerase II involved in managing tangles during DNA replication. Doxorubicin causes cardiotoxic side effects in 5-10% of cancer patients. D r Timm's research is trying to elucidate the mechanism behind this toxic effect. Assessing cardiac metabolism with hyperpolarized magnetic resonance shows promise in detecting cardiotoxic effects before damage which could improve cancer patient care in the future.
This synthetic molecule (Neurobiotin) is a derivative of a natural chemical, biotin, also known as Vitamin B7. The vitamin whose name refers to life (bio) is used in our cells for a wide range of metabolic processes. This synthetic derivative can be introduced into single brain cells in order to study their internal architecture and trace the fine processes axons and dendrites within and across different brain regions, revealing hidden details of the cellular diversity of the nervous system.
This amino acid (Homocysteine) is not part of the protein backbone but is formed in metabolism. Normally vitamin B12, B6 and B9 (folate) are in volved in removing excess homocysteine. High blood levels are associated with many adverse outcomes, including heart disease, stroke and dementia. Lowering homocysteine by giving B vitamins can help prevent these diseases.