Institute of Integrative Biology
Institute of Integrative Biology
News Article | May 9, 2017
LIVERPOOL, 09-May-2017 — /EuropaWire/ — Scientists from around the world are being led by the University to look at new ways of dealing with digestive issues in people living with cystic fibrosis. Cystic Fibrosis (CF) is an inherited genetic condition that affects over 10,500 people in the UK. Symptoms begin in childhood and slowly progress to destroy the lungs and digestive system. Half of people that die from cystic fibrosis are aged under 29 Distal intestinal obstructive syndrome (DIOS) is a common issue among people with cystic fibrosis, requiring hospital treatment and even surgery. Leading charity, the Cystic Fibrosis Trust has launched a new Strategic Research Centre, led by Professor Shirazi-Beechey, from the University’s Institute of Integrative Biology, to find new treatments to prevent DIOS and related intestinal issues for people living with the condition. Researchers from the academic and medical institutions in the UK, The Netherlands, Germany and Israel will combine experience and expertise to find a way of preventing the cells lining the gut from removing as much water and sodium from the digested matter, in order to increase the amount of fluid left to help its flow through the body. To do this, they will use lab-grown mini-guts called ‘organoids’. Professor Shirazi-Beechey, the Principal Investigator, said: “I am very grateful to the Cystic Fibrosis Trust for funding this project. We can’t wait to get started and see how we can apply some exciting new techniques to the issues affecting the digestive system of people with cystic fibrosis, which we know could make a big difference to their lives.” Dr Paula Sommer, Head of Research at the Cystic Fibrosis Trust, said: “This project is special because at the end, researchers hope to run a clinical trial on the best treatment, meaning that we could make real progress in the fight to restore digestive comfort to everyone with cystic fibrosis.”
News Article | March 31, 2016
With global food and energy security one of the greatest challenges of the 21st century, the new findings could help inform the design and engineering of new nanotechnologies to improve crop yields and biomass production. Cyanobacteria, often known as blue-green algae, are among the most abundant organisms in oceans and fresh water. They are similar to green plants because they can use the energy from sunlight to make their own food through photosynthesis. However, unique to cyanobacteria are intracellular structures called carboxysomes that allow them to convert carbon dioxide to sugar – a process known as carbon fixation – significantly more efficiently than many crops can. Carboxysomes are made of polyhedral protein shells and contain the enzymes required for the bacteria to fix carbon during the Calvin cycle stage of photosynthesis. Little is known about how these nano-scale 'machines' are produced or how they are regulated to adjust to environmental changes, such as light intensity. In a new study, published in Plant Physiology, researchers from the University's Institute of Integrative Biology attached fluorescent tags to carboxysomes and then used a fluorescence microscope to watch them in action within individual cells. By experimentally altering the amount of light available during cell growth the researchers observed how cyanobacteria regulate carbon fixation activity by changing the amount of carboxysomes in cells. The researchers also used chemical inhibitors that modify metabolism to monitor how this affects the distribution pattern of carboxysomes. They found that carboxysomes can either spread out or sit in the central line of the rod-shaped cell, depending on the redox states of electron transport pathways induced by the inhibitors. In collaboration with Dr Steve Barrett from the University's Department of Physics, the team developed a method to statistically analyse hundreds to thousands of bacterial cells from the microscope images. Co-author Dr Fang Huang, said: "It's exciting that through this technique we can now monitor, in real time, how bacteria modulate carboxysomes to maximise their carbon-fixing capacity. Our findings also provide some new clues about the relationship between the positioning of carboxysomes and cell metabolism." Carboxysomes are of interest to synthetic biologists and bioengineers, who hope to find ways to utilise their energy-boosting potential in food and biofuel production. Dr Luning Liu, lead author of the research, said: "Introducing cyanobacterial carboxysomes into plant chloroplasts could potentially improve the efficiency of photosynthesis and thereby the biomass yields. "There's still a lot we need to learn before their potential can be exploited. At this stage, we're just starting to understand how these fascinating cellular machines work, and this study marks another important step forward in this process." Explore further: Scientists discover how ocean bacterium turns carbon into fuel (w/ Video) More information: Light modulates the biosynthesis and organization of cyanobacterial carbon fixation machinery through photosynthetic electron flow. Plant Physiology, doi: dx.doi.org/10.1104/pp.16.00107
News Article | April 1, 2016
Scientists at the University of Liverpool have tracked how microscopic organisms called cyanobacteria make use of internal protein “machines” to boost their ability to convert carbon dioxide into sugar during photosynthesis. With global food and energy security one of the greatest challenges of the 21st century, the new findings could help inform the design and engineering of new nanotechnologies to improve crop yields and biomass production. Cyanobacteria, often known as blue-green algae, are among the most abundant organisms in oceans and fresh water. They are similar to green plants because they can use the energy from sunlight to make their own food through photosynthesis. However, unique to cyanobacteria are intracellular structures called carboxysomes that allow them to convert carbon dioxide to sugar — a process known as carbon fixation — significantly more efficiently than many crops can. Carboxysomes are made of polyhedral protein shells and contain the enzymes required for the bacteria to fix carbon during the Calvin cycle stage of photosynthesis. Little is known about how these nanoscale “machines” are produced or how they are regulated to adjust to environmental changes, such as light intensity. In a new study, published in Plant Physiology, researchers from the University’s Institute of Integrative Biology attached fluorescent tags to carboxysomes and then used a fluorescence microscope to watch them in action within individual cells. By experimentally altering the amount of light available during cell growth the researchers observed how cyanobacteria regulate carbon fixation activity by changing the amount of carboxysomes in cells. The researchers also used chemical inhibitors that modify metabolism to monitor how this affects the distribution pattern of carboxysomes. They found that carboxysomes can either spread out or sit in the central line of the rod-shaped cell, depending on the redox states of electron transport pathways induced by the inhibitors. In collaboration with Dr. Steve Barrett from the University’s Department of Physics, the team developed a method to statistically analyze hundreds to thousands of bacterial cells from the microscope images. Co-author Dr. Fang Huang says, “It’s exciting that through this technique we can now monitor, in real time, how bacteria modulate carboxysomes to maximize their carbon-fixing capacity. Our findings also provide some new clues about the relationship between the positioning of carboxysomes and cell metabolism.” Carboxysomes are of interest to synthetic biologists and bioengineers, who hope to find ways to utilize their energy-boosting potential in food and biofuel production. Dr. Luning Liu, lead author of the research, says, “Introducing cyanobacterial carboxysomes into plant chloroplasts could potentially improve the efficiency of photosynthesis and thereby the biomass yields. “There’s still a lot we need to learn before their potential can be exploited. At this stage, we’re just starting to understand how these fascinating cellular machines work, and this study marks another important step forward in this process.” The project was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and a Royal Society University Research Fellowship.
News Article | February 16, 2017
The University of Liverpool, in partnership with AKL Research and Development Ltd, is to lead on a clinical trial to test a potential new drug treatment for osteoarthritis. Osteoarthritis (OA) is the most common type of arthritis in the UK, affecting more than eight million people*, and is the leading cause of joint pain and stiffness in older people. As part of their research and development programme, AKL identifies promising phytochemicals, found in natural products, which are capable of being synthesized. Trials have identified two molecules which act synergistically and have been brought together to create 'APPA', a patented drug. In a variety of pre-clinical animal testing trials, APPA has clearly demonstrated significant pain relief from OA, improved functionality and the slowing of cartilage destruction. Having successfully passed preclinical toxicology studies, formal human studies can now start. The clinical trial is due to commence shortly at the Liverpool Clinical Trials Unit (LCTU) led by rheumatologist Professor Robert Moots from the University's Institute of Ageing and Chronic Disease. Professor Moots, said: "The severe pain from OA is usually managed with prescription drugs that are often not effective and that also, in many cases, induce unacceptable side effects. In many cases, major joint replacement surgery is needed to help deal with the pain. This is surely wrong. "This drug has huge potential to provide an effective treatment for OA. A reliable and easy way to treat OA has clear potential to save large amounts of money for the NHS and greatly improve the lifestyle and health of patients. "Working with research and development companies like AKL is crucial for the development and introduction of new treatments to benefit patients now and in future generations. We are excited to move this programme of trials forward." Research on how APPA affects human cells, especially activated neutrophils, is being led by Professor Steven Edwards at the University's Institute of Integrative Biology. Professor Edwards, said: "Neutrophils are the most abundant type of white blood cells and form an essential part of our immune system. There is now considerable evidence to show that neutrophils are activated in inflammatory diseases. They are however a "two-edged sword": they are required to protect us from infections but their inappropriate activation can result in irreversible damage in inflammatory diseases. "The 'holy grail' of anti-inflammatory targeting of neutrophils is specifically to block their tissue-damaging activities, but not compromise their ability to protect us. Work is ongoing but to date it appears that APPA does not target the host defence properties of neutrophils but does block their pro-inflammatory activities". David Sharples, CEO, AKL, said: "Professor Moots is leading this important clinical trial and that, in conjunction with Professor Edwards' research on APPA's novel modes of action, should provide the robust evidence we need to help bring this drug to market. There remains a high unmet need for an effective, well tolerated OA drug, so understandably we are very excited by APPA's prospects". AKL Research & Development Limited ("AKL") is an emerging pharmaceutical development company with a pioneering approach to drug development. AKL identifies and validates the active phytochemicals found in natural products. Synthetic versions of these compounds, whose safety and efficacy in their natural form have already been established in non-prescription markets are then taken to proof of concept through robust clinical evaluation. AKL's strategy of using well-characterised active compounds considerably improves the chances of successfully completing preclinical toxicity studies, avoiding unexpected side effects and demonstrating efficacy. It is AKL's intention to access global markets via a partner following proof of concept. The Company is based at the Stevenage Bioscience Catalyst, Stevenage, Herts UK. http://www. Professor Moots combines his clinical work as a consultant rheumatologist at Aintree University Hospital, with internationally recognised research into the causes and treatment of rheumatic diseases. Recently his group has been designated as a European Centre of Excellence for Rheumatology Research. Professor Steven Edwards is the Professor of Biochemistry at the Institute of Integrative Biology, University of Liverpool.
Pedersen A.B.,Institute of Evolutionary Biology and Center for Immunity |
Fenton A.,Institute of Integrative Biology
Trends in Parasitology | Year: 2015
It has become increasingly clear that parasites can have significant impacts on the dynamics of wildlife populations. Recently, researchers have shifted from using observational approaches to infer the impact of parasites on the health and fitness of individuals to using antiparasite drug treatments to test directly the consequences of infection. However, it is not clear the extent to which these experiments work in wildlife systems, or whether the results of these individual-level treatment experiments can predict the population-level consequences of parasitism. Here, we assess the results of treatment experiments, laying out the benefits and limitations of this approach, and discuss how they can be used to improve our understanding of the role of parasites in wildlife populations. © 2015 The Authors.
News Article | November 24, 2015
Usually, when female flies mate with multiple males, the last male fathers most of the offspring, with several other males fathering the rest. However, scientists have found that the outcome of this 'sperm competition' reverses when mating takes place prior to winter hibernation, with only the first male fathering any offspring. In the wild, females of many species can store sperm in their bodies for months before fertilisation takes place, often during periods of environmental stress, such as cold winters. The team, in collaboration with the Universities of Exeter and Vienna, examined the outcome of long term sperm storage in the fruit fly Drosophila pseudoobscura, by simulating the conditions in which females survive over winter. In a controlled experiment, virgin females were mated with two males each, and then stored for up to 120 days at 4°C. The outcome of sperm competition was consistent when sperm was stored for 0, 1 or 30 days, with the second male fathering most of the offspring. However, when females were stored in the cold for 120 days, the second male fathered less than 5% of the offspring. Moreover, when sperm were stored long term the first male fathered almost all offspring, even when carrying a genetic disease that usually reduces their reproductive success. Evolutionary biologist Dr Tom Price, from the University's Institute of Integrative Biology, who led the study said: "While further work is needed to establish exactly why this occurs, we suspect that the female stores sperm from the first male in a storage organ that offers protection against the cold, while subsequent sperm are stored elsewhere and get killed off by the drop in temperature." Long term survival of sperm over cold, hot or dry periods could explain some of the puzzling variation seen in sperm and sperm storage across the natural world. Dr Price added: "Sperm cells can range in size from 0.0005cm in humans to 5cm in some flies, and females of different species have really diverse ways of storing sperm, but we don't understand why. Existing sperm competition research has focused on short term sperm storage, so may have missed a key process driving the evolution of sperm and sperm stores." Additionally, the observation that promiscuous females become effectively monogamous when winters get cold enough could impact on some pest control strategies. Dr Price explained: "One of the best methods for controlling serious pest insects is the sterile male technique, which sees laboratory-bred sterile males released to mate with wild females. The problem in promiscuous species, however, is that females can just continue to mate until they find a fertile male, so the technique fails. "Our finding suggests that releasing sterile males just before winter could prevent this, as provided a female mates with a sterile male first then no offspring will be produced the following spring. As males normally don't survive winter, this means the pest population can be dramatically reduced." 'The Winter is Coming: hibernation reverses the outcome of sperm competition in a fly' is published in the Journal of Evolutionary Biology. Explore further: Fathering offspring is more than just a race to the egg More information: Paulina Giraldo-Perez et al. Winter is coming: hibernation reverses the outcome of sperm competition in a fly, Journal of Evolutionary Biology (2015). DOI: 10.1111/jeb.12792
Willi Y.,University of Neuchatel |
Willi Y.,Institute of Integrative Biology
American Naturalist | Year: 2013
Outcrossing creates a venue for parental conflict. When one sex provides parental care to offspring fertilized by several partners, the nonproviding sex is under selection to maximally exploit the caring sex. The caring sex may counteradapt, and a coevolutionary arms race ensues. Genetic models of this conflict include the kinship theory of genomic imprinting (parent-of-origin-specific expression of maternal-care effectors) and interlocus conflict evolution (interaction between male selfish signals and female abatement). Predictions were tested by measuring the sizes of seeds produced by within-population crosses (diallel design) and between-population crosses in outcrossing and selfing populations of Arabidopsis lyrata. Within-population diallel crosses revealed substantial maternal variance in seed size in most populations. The comparison of betweenand within-population crosses showed that seeds were larger when pollen came from another outcrossing population than when pollen came from a selfing or the same population, supporting interlocus contest evolution between male selfish genes and female recognition genes. Evidence for kinship genomic imprinting came from complementary trait means of seed size in reciprocal between-population crosses independent of whether populations were predominantly selfing or outcrossing. Hence, both kinship genomic imprinting and interlocus contest are supported in outcrossing Arabidopsis, whereas only kinship genomic imprinting is important in selfing populations. © 2013 by The University of Chicago.
Guillaume F.,Institute of Integrative Biology |
Otto S.P.,University of British Columbia
Genetics | Year: 2012
Pleiotropy is the property of genes affecting multiple functions or characters of an organism. Genes vary widely in their degree of pleiotropy, but this variation is often considered a by-product of their evolutionary history. We present a functional theory of how pleiotropy may itself evolve. We consider genes that contribute to two functions, where contributing more to one function detracts from allocation to the second function. We show that whether genes become pleiotropic or specialize on a single function depends on the nature of trade-offs as gene activities contribute to different traits and on how the functionality of these traits affects fitness. In general, when a gene product can perform well at two functions, it evolves to do so, but not when pleiotropy would greatly disrupt each function. Consequently, reduced pleiotropy should often evolve, with genes specializing on the trait that is currently more important to fitness. Even when pleiotropy does evolve, not all genes are expected to become equally pleiotropic; genes with higher levels of expression are more likely to evolve greater pleiotropy. For the case of gene duplicates, we find that perfect subfunctionalization evolves only under stringent conditions. More often, duplicates are expected to maintain a certain degree of functional redundancy, with the gene contributing more to trait functionality evolving the highest degree of pleiotropy. Gene product interactions can facilitate subfunctionalization, but whether they do so depends on the curvature of the fitness surface. Finally, we find that stochastic gene expression favors pleiotropy by selecting for robustness in fitness components. © 2012 by the Genetics Society of America.
News Article | March 12, 2016
A giant rat nearly the size of a 4-year-old child has reportedly been found in East London, although some skeptics are critical of the story. The giant rodent was supposedly found near a children's playground in Britain's capital city. Tony Smith, a 46-year-old gas engineer, first reported seeing the massive rat in near a block of apartments. He supposedly found the deceased body of the rat laying next to a bush in the children's play area. The man claims the rat weighed an astonishing 24 pounds. Some viewers on social media claimed a photo taken of the rat being held by Smith's friend James Green is deceiving. Some say the surprising apparent size of the rodent is the result of forced perspective, which makes the animal look larger than normal. One skeptic claims to have measured the size of the rodent, finding it to measure just 2 feet long, half the length claimed by Smith. Brown rats that live underneath the streets of London are typically about 10 inches in length. But by placing the rat nearer the camera, it is possible to make the rodent look larger than it is in real life. The same effect of forced perspective is used when tourists in Italy were photographed to look like as if they are keeping the Leaning Tower of Pisa from falling to the ground. "No way a brown rat would be that big, or that anyone could pick up a rat of 11 kg (24 pounds) with a litter picker. There are several hoaxes showing rats like this online or previously published in newspapers. Even a Gambian pouched rat, which is 3 ft long, only weighs around 1.5 kg (3 pounds)," said Jane Hurst of the Institute of Integrative Biology at the University of Liverpool. Brown rats tend to keep to themselves, shying away from people. However, the men who say they discovered the giant rodent say trash bins accompanying nearby apartments are often left open, providing wild animals there with a plentiful source of food. While some people claim the giant rat seen in the photograph is the result of an optical illusion, pest control company Rentokil theorizes the animal may be a freak of evolution. The debate rages on, as people take one side or another in the case of the mysterious giant rat.
News Article | December 24, 2015
(Phys.org)—Two large international teams of researchers have conducted two separate analysis of the nature of plants and each has found something new. Both teams have had their work published in the latest issue of the journal Nature—the first looks at trait commonalities among plant forms that allow for surviving natural selection. The second looks at the traits that are responsible for giving plants a competitive advantage. Jonathan Levine of the Institute of Integrative Biology in Switzerland, offers a News & Views piece on the work done by the two teams and explains why such studies are becoming more important as scientists attempt to predict how plants may fare in light of global warming.