Dr Giles Yeo to deliver talk at School of Life Sciences, University of Lincoln

Dr Giles Yeo, from the University of Cambridge, Horizon and the BBC’s “Trust me I’m a Doctor” will be providing an informed and entertaining seminar titled “The genetics of obesity: Can an old dog teach us new tricks?” on Friday 4th May 1-2 pm, in the School of Life Sciences seminar series at the Joseph Banks Laboratories (JBL3C01).

Dr Yeo is a geneticist with nearly 20 years’ experience studying obesity and the brain control of food intake. He obtained his PhD from the University of Cambridge in genetics in 1998 (studying the genetics of the fugu fish) and has been there ever since. He was in the initial vanguard that described a number of genes that when mutated, resulted in rare forms of severe obesity, thus uncovering key pathways in the brain that control food intake.

Dr Giles Yeo
Dr Giles Yeo

His current research focuses on understanding how these pathways differ between lean and obese people, and the influence of genes in our feeding behaviour. Giles also presents science documentaries for the BBC. His critically acclaimed investigative piece ‘Clean eating – The dirty truth’, for BBC Horizon, was screened in January 2017 and prompted an important national debate about dieting advice and evidence-based science. More recently he featured weekly on BBC2’s ‘Trust Me I’m a Doctor’ as one of the new ‘doctors’.

For more details contact Professor Jon Whitehead (jwhitehead@lincoln.ac.uk). (Please note, this talk is open to staff and students only).

Know your Chardonnay from your Chablis? Scientists reveal new secrets to regional wine variation

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New research has shown for the first time how tiny genetic differences in a single microbe help to produce the distinctive variations in taste and odour between wines from different regions.

It was previously thought that wines produced from the same variety of grape by different vineyards get their geographic signature because of environmental factors such as local soil conditions, climate and agricultural practices.

However a new study by biologists from the University of Lincoln, UK, and the University of Auckland, New Zealand, has revealed how sub-populations of a microbe at the heart of the wine-making process can substantially alter the characteristics, or terroir, of the finished product.

Microbes are single-cell organisms found everywhere on the planet. Most belong to one of four major groups: bacteria, viruses, fungi, or protozoa. This new investigation explored how genetically different populations of the main microbe used in the fermentation process during wine-making – the Saccharomyces cerevisiae yeast – affects the flavour and aroma of a wine. Much of the character of a wine comes from chemical compounds produced as by-products during fermentation, when sugars from the grapes are converted into alcohol.

The researchers investigated six different populations of the yeast from six major wine growing regions in New Zealand. Using Sauvignon Blanc grapes, they found that concentrations of 39 different compounds derived from yeast during the fermentation process affect the flavour and aroma of wine; 29 of these compounds vary depending on which region the yeast originated from.

Dr Matthew Goddard, Reader in the School of Life Sciences at the University of Lincoln, designed the research and co-authored the resulting paper, published in the academic journal Scientific Reports, alongside lead researcher Sarah Knight from the University of Auckland. The study builds on Dr Goddard’s previous work in New Zealand, which for the first time showed that microbes associated with vineyards and wines differ from region to region.

Dr Goddard said: “We believe that this is the first direct experimental evidence showing that microbes help define why you get different wine in different places, or the idea of terroir. The regional distinctiveness of wine plays a major part in its value, and there is a lot of interest in what drives terroir. Classically it was thought that it was down to climate and soils, but our research shows biology also plays a part.

“These findings could be very important because if this is true for wine, it may also be true for other agricultural crops.”

The researchers believe that their study could have wide-ranging implications for sustainable agriculture. Until now, microbes have largely been overlooked as a potential driver behind the different geographic phenotypes (physical characteristics) of crops, but these findings highlight the importance of characterising and understanding biodiversity and the services it may provide.

Dr Goddard added: “With a better understanding of the forces driving microbial population and community differentiation, food and agriculture sectors can develop systems to better control and manage these communities, helping to conserve the regional identity of products and hopefully crop health and productivity. We already know that distinct regional variations can have a significant impact on the value of a product and moreover, the methods of farming which maintain different bio-diversities are more desirable as they promote responsible environmental stewardship.”

The study concludes that further investigations are now needed to identify whether other species of fungi and bacteria may also contribute to regional characteristics. Dr Goddard specialises in the study of these patterns and processes and he will continue his investigations as part of the Lincoln Institute for Agri-Food Technology, a research institute recently launched by the University of Lincoln to help improve efficiency and sustainability, and to reduce waste throughout the food pipeline, from farm to retailer.

Breakthrough for debilitating heart and lung disease

British Heart Foundation logo British Heart Foundation logo A protein that targets the effects of a faulty gene could offer the first treatment targeting the major genetic cause of Pulmonary Arterial Hypertension (PAH), according to research funded by the British Heart Foundation (BHF).

Genetic evidence dating back to 2000, from research the BHF helped to fund, indicated that the absence or reduced activity of a particular protein, bone morophogenetic protein type II receptor (BMPR-II), leads to PAH. BMPR-II is important to the normal function of the blood vessels of the lungs. PAH is thought to affect around 6,500 people in the UK.

This new study led by BHF Professor of Cardiopulmonary Medicine Nick Morrell and including expertise from Dr Rajiv Machado at the University of Lincoln, UK, is the first to use a protein, called BMP9, to reverse the effects of reduced activity of BMPR-II and to reverse the disease itself. The study was conducted in mice and rats, but also using cells from patients with PAH. It is published today in Nature Medicine.

PAH is a chronic and debilitating disease that affects the blood vessels in the lungs, leading to heart failure, and leaves sufferers feeling breathless and exhausted. Current treatments only target the symptoms and prognosis remains poor. The only effective cure is a lung, or heart and lung, transplant, which has associated risks and complications.

Once diagnosed with PAH, a person has a 30 per cent chance of dying within three years and the condition affects more women than men. Researchers speculate that this gender disparity is caused by pregnancy triggering the disease in genetically susceptible women or that oestrogen can affect the function of BMPR-II.

A team at the University of Cambridge, with contributions from researchers at the University of Lincoln, Switzerland and the US, searched for a BMP protein that could enhance the function of BMPR-II to target the condition. The researchers firstly trialled different BMP proteins on lung blood vessel cells grown in a dish. This process showed BMP9 to be most selective, and therefore less likely to have negative effects on other cells.

This study used the first animal model, a mouse, which closely mimics the human genetic form of the disease. The University of Lincoln’s Dr Machado was instrumental in designing the strategy for development of this experimental model employed in the study.

Using a specific set of molecular tools, Dr Machado replicated a mutation frequently observed in human PAH patients which, subsequently, was introduced into the mouse genome. This facilitated the generation of a mouse model that naturally mirrored the human disease state critical for the assessment of therapeutic options.

Ultimately, the team showed that BMP9 treatment reversed PAH in three separate mouse and rat models. They found that the treatment works in mice with both the genetic from of the disease, and in acquired forms of PAH, where the cause is unknown.

BHF Professor Nick Morrell, who led the research, from the Department of Medicine at the University of Cambridge School of Clinical Medicine, and Director of the BHF Cambridge Centre for Cardiovascular Research Excellence, said: “The next step for our research is studies in people with pulmonary arterial hypertension – first, safety testing to ensure the compound can be given to people. But we’re confident of passing this phase because BMP9 exists naturally in the body. We’re just giving patients more of it.”

Professor Jeremy Pearson, Associated Medical Director of the British Heart Foundation, which funded the research, said: “We’re very excited by these results. This condition is horrible and an effective treatment that prevents the need for a transplant would be a game-changer. Clinical trials of the treatment in patients are still needed but these findings, from years of research supported by the BHF, offer real promise of a cure.”

One gene closer to helping sufferers of rare genetic disorder

A new study has separately confirmed and significantly built on recent research, identifying mutations of a gene that causes the uncommon but potentially fatal Adams-Oliver syndrome.

A leading team of medical and genetics experts from institutions across Europe independently identified a gene called NOTCH1 while also discovering the largest range of mutations, both consolidating and expanding previous research published in 2014.

The new findings, published in the journal Circulation: Cardiovascular Genetics, solidify Notch signalling as a major factor in Adams-Oliver syndrome (AOS) and further advance diagnosis and treatment of this neonatal disorder – characterised by limb and scalp defects, accompanied by a host of cardiac and vascular complications.

The identification of the gene was driven by Professor Richard Trembath and Dr Laura Southgate, from Queen Mary University of London, with subsequent functional analyses primarily conducted by Dr Rajiv Machado and colleagues at the University of Lincoln, UK.

The study’s joint senior author Dr Machado, from the School of Life Sciences, University of Lincoln, said: “Our study, which provides the largest collection of NOTCH1 mutations to date, clearly places this gene as a major causal genetic factor in AOS and in particular when associated with major cardiovascular defects, both developmental and structural.

“This insight into NOTCH1 offers the potential to explain its function in the development of key systems in the body – notably cardiovascular, skeletal and pulmonary systems. The ultimate hope is further research in this area will result in more effective diagnoses, but most importantly treatment therapies, for those affected with this debilitating condition.”

The initial gene identification process was based on sequencing the genomes of 12 families affected with AOS. They found that two people from different families had mutations in the NOTCH1 gene. Confirmation of these findings was obtained by screening a cohort of 52 additional patients, which led to the identification of a further eight unique mutations.

This study, combined with the earlier publication of NOTCH1 mutations in AOS, is a significant breakthrough in the understanding of this developmental disorder, which currently has no cure.

In 2011, Dr Machado and Dr Southgate were integral to efforts that led to the discovery of the ARHGAP31 gene – the first identified molecular defect associated with AOS. This finding was noted by international publications including the American Journal of Medical Genetics which provided an editorial to mark the work.

Since then four additional genes, including NOTCH1, have been identified indicating this is a disease underpinned by multiple genetic factors.

The collaboration is currently further examining the impact of NOTCH1 mutations described in this study and exploring the possibility of additional mutations in as yet unidentified genes in an extensive cohort of patients.

This work was supported by the British Heart Foundation, the German Research Foundation and a Wellcome Trust Strategic Award.

Dolphins set up home in the Mediterranean after the last Ice Age

The bottlenose dolphin only colonised the Mediterranean after the last Ice Age – about 18,000 years ago – according to new research.

Leading marine biologists collaborated in the study – the most detailed ever conducted into the genetic structure of the bottlenose dolphin population in the Mediterranean to date – and the results have been published today 17th February, 2015 in the journal Evolutionary Biology.

Tissue samples from 194 adult bottlenose dolphins (Tursiops truncatus) were collected between 1992 and 2011 from the five main eastern Mediterranean basins.

The team’s aim was to investigate the population structure and historical processes that may be responsible for the geographic distribution of the species in that area. No other study has compared the fine scale genetic structure within the Mediterranean, with the well described genetic structure in the North Atlantic.

The Mediterranean basin in particular is a global biodiversity hotspot and several marine species exhibit complex population structure patterns over relatively short geographic distances. It is therefore a particularly interesting region for scientists to investigate the drivers of population structure in marine organisms.

One of the study’s lead authors Dr Andre Moura, from the School of Life Sciences, University of Lincoln, UK, said: “As a consequence of the bottlenose dolphin only colonising the Mediterranean after the last glacial maximum or Ice Age, population structure in the Mediterranean mainly arises from the different colonisation routes the various early colonisers took, and the genetic varieties they carried.

“Similar to the North Atlantic, two ecological types are likely to exist, one occupying deep ‘pelagic’ – or away from the coast – waters, and another occupying ‘coastal’ shallow water areas. By comparing our results with genetic data from previous studies on Atlantic bottlenose, we concluded that bottlenose dolphin in the North Atlantic, Mediterranean and North Sea are likely to represent a single metapopulation – This is a particular type of population structure, when a single population is subdivided into regional subgroups that exchange individuals at varying rates. These results have important implications for the understanding and conservation of Mediterranean biodiversity.”

‘Drivers of Population Structure of the Bottlenose Dolphin (Tursiops truncatus) in the Eastern Mediterranean Sea’ Evolutionary Biology Stefania Gaspari, Aviad Scheinin, Draško Holcer, Caterina Fortuna, Chiara Natali, Tilen Genov, Alexandros Frantzis, Guido Chelazzi, André E. Moura DOI 10.1007/s11692-015-9309-8