Integrative Physiology Theme Day Talks and Photos
anant parekh: targeting store-operated crac channels in nasal disease
In the opening session, chaired by Professor David Paterson, the first talk of the day was given by Professor Anant Parekh FRS. Prof Parekh described a major role for store-operated calcium channels in sustaining mast cell activation. Mast cells respond to a variety of allergens and are causally linked with a range of diseases including allergies, nasal polyposis and asthma. Using acutely isolated human tissue from patients with severe allergies and nasal polyps, Anant’s Group demonstrated that targeting store operated calcium channels reduced the extent of immune cell activation. Targeting these channels would therefore be a new therapeutic strategy for combating a range of immune disorders.
LISA HEATHER: the battle between hypoxia and diabetes: an alternative role for metabolism in cardiovascular disease
Second to present was Associate Professor Lisa Heather. Her Group works on understanding why type 2 diabetes, a disease of abnormal metabolism, impairs the hearts ability to function after a heart attack. Their research has shown that the increased fatty acids that circulate in the blood in diabetes inhibit an important transcription factor called the Hypoxia Inducible Factor (HIF), which is critical after a heart attack. In addition, drugs that activate HIF improve the function of the heart in diabetes.
ying-chi chao: unique regulation of camp signals within myofilaments in rat cardiac myocytes
Next to present was Dr Ying-Chi Chao, a Postdoctoral Research Scientist working in the Zaccolo Group. He revealed that in cardiac myofilament, troponin I and myosin binding protein C are regulated by distinct cAMP pools. By uncovering this compartmentalised regulation, Dr Chao and his team might be able to target a new pharmacological strategy to treat diastolic dysfunction.
elizabeth haythorne: how hyperglycemia impairs beta cell function
The last talk of the session was given by Dr Elizabeth Haythorne, a Postdoctoral Research Scientist working in the Ashcroft Group, who was recently published in Nature Communications. Type 2 diabetes arises when pancreatic β-cells fail to secrete adequate amounts of insulin in order to maintain blood sugar levels within a normal, healthy range. The underlying mechanisms behind why this happens is not well understood. Mitochondria are intracellular organelles which are responsible for generating energy from fuels, such as glucose. Healthy mitochondria are essential for β-cells to secrete insulin in response to a rise in blood sugar. Using a combination of techniques to examine functional, protein and gene changes, Dr Haythorne and her team have found that prolonged hyperglycaemia/diabetes impairs mitochondrial metabolism and energy production in pancreatic β-cells. They propose that this underlies the progressive failure of β-cells in diabetes.
samira lakhal-littleton: the cell-autonomous hepcidin/ferroportin axis: a novel and essential pathway of iron homeostasis in the cardiovascular system
After a break, the second session commenced, chaired by Associate Professor Heidi de Wet. The first talk was given by Associate Professor Samira Lakhal-Littleton, who outlined her Group's latest research, some of which was recently published in PNAS. Iron deficiency is the most common nutritional deficiency in the world. It can sometimes lead to anaemia. Until recently, little was known about the effects of iron deficiency without anaemia. Work from Prof Lakhal-Littleton and her team has shown that iron deficiency without anaemia can impair cardiovascular function. This work supports the notion that iron deficiency in itself should be a therapeutic target in cardiovascular disease.
pawel swietach: what's new in ph physiology?
Next, the audience heard from Associate Professor Pawel Swietach. The Swietach Lab studies acid-base balance (pH) in health and disease. In his talk, Prof Swietach presented the three pillars of his group's research: cancer, cardiac and red blood cells. Acidity is a chemical signature of solid tumours, acting as a selection pressure that influences disease progression by selecting those cellular phenotypes that thrive under acid stress. Such phenotypes tend to make the disease more aggressive, so the team are actively seeking the molecular mechanisms that render a cancer cell acid-resistant, and how to exploit this information therapeutically. In the area of cardiac research, they are studying how pH affects various biological processes that are key to cardiac function, focusing their efforts on understanding how changes in pH affect cellular growth (hypertrophy), a process that may lead to heart failure if aberrantly activated. Finally, they have an interest in the biophysics of red blood cells, focusing on how cytoplasmic tortuosity and cell shape affect gas exchange function, giving them new information about hematological conditions, such as hereditary spherocytosis. Prof Swietach also introduced their identification of novel biomarkers of hemolysis, offering a new method for monitoring hemolytic crisis.
Shih-jung fan: glutamine deprivation regulates cancer exosome origin and functions
Next up was Dr Shih-Jung Fan, a Postdoctoral Research Scientist working in the Goberdhan Group. Dr Fan presented his latest research on the small informative packages sent by cancer cells to overcome their hostile microenvironment.
maike glitsch: coincidence detection of membrane stretch and extracellular ph by the proton sensing receptor ogr1
Next, Associate Professor Maike Glitsch talked about her Group's recent findings identifying the proton-sensing G protein coupled receptor OGR1 as a coincidence detector of extracellular pH and cell stretch that requires both sufficient extracellullular acidification and membrane stretch to be active.
SARAH DE VAL: ATHENA SWAN IN DPAG
Athena SWAN Academic Lead Associate Professor Sarah De Val was the final speaker before breaking for lunch, reminding the Department's Researchers of the Athena SWAN initiatives in place and how these can help and support them. She also encouraged everyone to sign up for the Department's new in-house Implicit Bias workshop, and to get involved with the newly established departmental working groups designed to enrich staff and student experiences at DPAG.
michael puljung: spectroscopic studies of katp channel gating
After lunch, in the third session of the day chaired by Professor Helen Christian, the audience heard from Dr Michael Puljung, a Postdoctoral Research Scientist working in the Ashcroft Group. Dr Puljung's talk highlighted how he uses light and voltage as sensitive probes of the structure and function of the ATP-sensitive potassium channel, an important trigger for insulin secretion and target of drugs used to treat diabetes.
heidi de wet: orphan abc transporters - the secret life of abcc5
Next up was Associate Professor Heidi de Wet. A large number of genes are involved in the regulation of energy metabolism in mammals and the recent advances in RNAseq technologies allow GWAS studies to identify new susceptibility genes more rapidly than ever before. A recent GWAS study identified an orphan ABC transporter, ABCC5, as a new type 2 diabetes susceptibility gene and work in Prof de Wet's laboratory has shown that Abcc5 knock-out mice have less fat, were more insulin sensitive and secreted elevated levels of incretin hormones from their gut. The study received a lot of attention as it also highlights the close connection between the gut and the brain and the work has been selected as an Editors’ Choice article for the August issue of Obesity.
neil herring: neuropeptide y: being unsympathetic towards the heart
The penultimate talk of the day was given by Associate Professor Neil Herring, who presented data regarding the neurotransmitter Neuropeptide-Y (NPY) and how it can trigger dangerous heart rhythms in both animal models and patients. Drugs targeting NPY receptors may be useful in patients presenting with heart attacks, and measuring NPY levels in patients with heart failure may provide doctors with useful information on how severe a patient's condition may be.
donald bers: mitochondrial ca, hyperglycaemia and heart failure
Introduced by Professor Manuela Zazzolo, our Visiting Newton Abraham Professor Dr Donald Bers gave the concluding Keynote Talk of the day. He described how the mitochondrial calcium uniporter mediates small beat-to-beat Ca influx but integrates to help match energy supply to energy demands. He described transient permeability transition pore openings that may refresh rather than kill mitochondria. He showed how diabetic hyperglycaemia promotes myocyte oxidative stress via glycosylation of CaMKII. He closed with a story about how ketone bodies are well metabolized in normal hearts, but that in heart failure they can accumulate as polymers that cause mitochondrial dysfunction and limit energy production.