̽��ֱ�� of Cambridge - fruit fly

Opinion: Can organs have a sexual identity?

Anonymous — Wed, 24 Feb 2016 15:03:28 +0000

A new study published in Nature suggests that the stem cells that allow our organs to grow “know” their own sexual identity, and this influences how they function. These findings could explain why the prevalence of some diseases, such as certain cancers, differs between the sexes.

Beyond the obvious reproduction-related anatomical differences between males and females, many other organs also show sex specific characteristics, for example in the form of subtle differences in size or in their susceptibility to disease. ̽��ֱ��effect of hormones has been extensively researched, and can explain many of the differences. However, less is known about the potential impact of differences between the cells that created the organs themselves.

̽��ֱ��researchers found important genetic differences at the cellular level and also demonstrated how these differences impact organ growth, independently of circulating hormones. These findings could shed light on why some diseases prevail in men or women.

Regenerating gut cells

To uncover genes that regulate cellular differences between male and female organs, the group, led by Irene Miguel-Aliaga studied intestines of fruit flies. Fruit flies are good experimental systems to investigate gene function and, importantly, they exhibit clear sex-related traits such as body size (females are larger than males) and differences in gut physiology.

̽��ֱ��researchers hypothesised that the differences in size and gut physiology between the sexes might be due to intrinsic genetic differences at the cellular level. By monitoring the degree to which different genes were activated in both sexes, the researchers found that subgroups of genes regulating gut function were activated differently in male and female flies. This suggested that “sex-determination” genes (genes that are active due to sex chromosomes) inside gut cells were affecting organ function.

Gut cells are continuously regenerated by gut stem cells through cell division, in which the parent stem cell typically divides into a stem cell plus a specialised cell which will no longer divide but performs functions of the gut. Several mechanisms adjust stem cell divisions to suit the needs of the tissue (for example, if the gut is damaged, stem cells produce more cells to enable tissue regeneration).

By manipulating genes in the cells to act as more “male” or more “female” the authors demonstrated that sex-determinants endowed “female” intestinal stem cells with better ability to divide. This increased stem cell division resulted in longer and better regenerating female guts compared to male guts. Suppressing this “sex-determination path” specifically in intestinal stem cells of a female fly caused the gut to resemble that of a male fly, and activating it in intestinal stem cells of a male caused its gut to increase in size to that of a normal female fly. Further experiments identified additional links between sex-determinants and cell growth, providing a more complete picture.

Advantages and disadvantages

Higher rates of cell multiplication can have advantages for an organ, in that it can speed up the rate of repair after injury. In the female flies it improves nutrient absorption to accommodate high nutritional demands linked to reproduction. However, higher proliferation also leads to more rapid ageing, and higher vulnerability to tumours. Consistent with this view, the study showed that female flies were more prone to genetically-induced intestinal tumours than males; moreover, the researchers were able to confirm that suppressing the “feminising genes” reduced the ease with which tumours form in the gut of female fruit flies.

̽��ֱ��researchers therefore showed how sex-determining genes in stem cells can control organ function, independently of external hormone influences. This had consequences on organ size and also optimised reproduction in females but came with the risk of increased susceptibility to tumours.

̽��ֱ��findings have broad implications in the way we understand tissue maintenance, disease and ageing. Future work will be needed to investigate if the mechanisms discovered in the fruit flies' intestines are also seen in other tissues, and if they are applicable in mammals. If this is the case (which is considered probable), sex-related differences may affect how cells respond to treatments and so by understanding these differences we might be able to develop more effective therapies.

Golnar Kolahgar, ̽��ֱ��Gurdon Institute, Postdoctoral research associate, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Inset image: Drosophila immigrans face (John Tann).

Golnar Kolahgar (Gurdon Institute) discusses the suggestion that the stem cells which allow our organs to grow “know” their own sexual identity.

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Framed Embroidery Kidney

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Opinion: How fruit flies can help keep African scientists at home

Anonymous — Mon, 15 Feb 2016 12:01:02 +0000

̽��ֱ��humble fruit fly is being put to an unusual use in sub-Saharan Africa: it’s being used as bait. Its intended lure? It’s hoped that the tiny creature, whose scientific name is Drosophila melanogaster, can stop the exodus of researchers from Africa.

At the moment most of the biomedical research being done in African laboratories is performed using rats. Now a project called DrosAfrica is underway to promote the use of the fruit fly as a model organism for research into human diseases.

There are several reasons for this. Firstly, rats are far more expensive to keep than fruit flies. As an affordable alternative, the fruit fly requires fewer resources to maintain and not as much expensive preparation for experiments.

Also, as a model system, Drosophila enables researchers to perform sophisticated genetics, live imaging, genome-wide analysis and other state-of-the-art approaches. Drosophila research has identified thousands of genes with human equivalents. This has provided key insights into cancer biology, pathology, neurobiology and immunology.

Drosophila is a prime model organism with tens of thousands of researchers working on every aspect of their biology. This work is aided by electronic open resources such as Flybase and stock centres like the one in Bloomington, Indiana in the US. ̽��ֱ��centre will send Drosophila to any lab in the world for the cost of shipping. These stock centres are funded by governmental grants enabling 100 000s flies to be kept alive in warehouses.

And entire research unit has been built with a focus on understanding a specific aspect of the fly. ̽��ֱ��most famous is called Janelia Farm, founded by the Howard Hughes Medical Institute in the US.

A bigger agenda

̽��ֱ��project that’s using fruit flies as bait for scientists is known as DrosAfrica. It wants to drive the paradigm shift from rats to flies as experimental organisms. To do this, project leaders have organised workshops to share fruit fly techniques with universities and research institutes across sub Saharan Africa.

But there’s more to the work than merely extolling the virtues of fruit flies.

We also try to provide basic equipment such as dissecting microscopes, buffers, slides and antibodies for labelling proteins to facilitate the creation of local research communities. Such strong communities will ultimately be able to provide PhD programmes and research opportunities for African researchers. This will mean students don’t automatically feel they have to emigrate when seeking research opportunities.

Powerful local research programmes will also help to place the continent in the spotlight of international research. This could ultimately lead to a return of expatriates with a strong scientific background.

Activities organised by DrosAfrica: Past and Future

During the last three years, DrosAfrica has organised three workshops at the Institute of Biomedical Research Kampala International ̽��ֱ��-Western Campus, Uganda. Two focused exclusively on the use of Drosophila for biomedical research. ̽��ֱ��other concentrated on image and data analysis techniques.

Attendants and faculty members of the first DrosAfrica workshop ‘Drosophila in Biomedical Research: Affordable AND Impacting!’ (Summer 2013)

̽��ֱ��workshops' participants came from sub-Saharan Africa and included Nigerians, Kenyans, Ugandans and a delegate from South Sudan. They were able to work on several common projects and then networked after the workshops using information and resources on a dedicated website. These interactions planted the seed for developing an African Drosophila research community. At this institute, we’ve been lucky to build on the work that the non-profit organisation Trend has already done. Their team of volunteer scientists equipped the institute’s lab and introduced insect research models to the local scientists.

In 2016 the project plans to deliver workshops at Kenya’s International Centre of Insect Physiology and Ecology. ̽��ֱ��team is also visiting Nigeria during the second half of February to pave the way for future research collaborations.

̽��ֱ��work done over the past few years has already paid dividends. Alumni from the workshops have presented their work at international scientific conferences and supervised undergraduate, Masters and PhD projects. PhD candidates have graduated on the basis of their research done on flies. One student has submitted an abstract to the American Society for Biochemistry and Molecular Biology.

DrosAfrica vision

̽��ֱ��DrosAfrica project is taking important steps to increase the African contribution to scientific advancement. In the coming years we hope to further boost local research opportunities to promote genuine African research led by African researchers, all of them investigating matters of interest to Africans.

And to think: it all started with a tiny little fruit fly.

*DrosAfrica would like to acknowledge the generosity of Faculty members and sponsors, without whom the workshops described above wouldn’t have been possible. They are:

(Cambridge Africa, Sayansi, Wellcome Trust, TWAS, KIU, Pembroke College-Cambridge, St John’s College-Cambridge, Emmanuel College-Cambridge, EMBO, Fruit4Science, and very specially to FRS Tony Kouzarides).*

Silvia Muñoz-Descalzo, Lecturer in Biology & Biochemistry; Developmental Biology Theme, ̽��ֱ�� of Bath and Timothy Weil, Lecturer, Department of Zoology, ̽��ֱ�� of Cambridge

This article was originally published on ̽��ֱ��Conversation. Read the original article.

̽��ֱ��opinions expressed in this article are those of the individual author(s) and do not represent the views of the ̽��ֱ�� of Cambridge.

Timothy Weil (Department of Zoology) and Silvia Muñoz-Descalzo ( ̽��ֱ�� of Bath) discuss the project that aims to make the fruit fly a model organism for research in Africa.

Tim Weil and Anna York-Andersen, Weil Lab

Actin cables in Drosophila nurse cells during late-oogenesis. At this stage, nurse cells die and extrude their cytoplasm into the developing oocyte.

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African universities reap fruits of fly research

tdk25 — Fri, 10 Jul 2015 05:00:12 +0000

Drosophila melanogaster, better known as the humble fruit fly, has emerged as the unlikely basis of an attempt to help to stem a “brain drain” from African universities.

While they may be loathed by many as a relentlessly irritating pest, fruit flies are nevertheless being used as an ally by a team of researchers who believe that they could play a role in cultivating research talent in Africa, and in preventing its loss to the rest of the world.

Under a new project, called “DrosAfrica”, fruit fly research labs are being established at institutions in Uganda, Nigeria, and Kenya. ̽��ֱ��hope is that the training and research that these centres undertake will nurture a community of biomedical research scientists in Sub-Saharan Africa, and inspire other universities to follow suit.

Despite their unglamorous reputation, fruit flies are of great value to scientific research and have played an often overlooked role in some of the biggest biological breakthroughs of the past 100 years. As an example, the first jet-lag gene, the first learning gene and the first channel proteins were all identified in flies.

About 75% of known human disease genes have a recognisable match in the genome of fruit flies, and this makes them ideal for research on subjects such as cellular development and the causes of complex conditions, such as neurodegeneration, psychiatric diseases, and cancer.

In Africa, where postgraduate scientific research in universities is often limited by financial constraints, or a lack of resources and infrastructure, Drosophila could therefore be a valuable tool. They are, after all, both cheap and – as people working in the food or restaurant industries tend to know only too well – available in plentiful supply.

Dr Isabel Palacios, a Fellow of St John’s College, ̽��ֱ�� of Cambridge, and one of the founding academics behind DrosAfrica, argues that this could help to resolve a shortage of scientific talent emerging from the continent. African researchers make up only 2.2% of the world’s academic research community as a whole, and Sub-Saharan Africa contributes just 0.6%. Lacking the tools needed to undertake world-class research, many African researchers also leave their own countries and move to better-resourced institutions, leading to a “brain drain” effect that has deprived their home nations of skilled researchers.

“Students at African universities who start a PhD often find that they can’t really do much research and end up lecturing and teaching instead,” Palacios said. “Our big idea is to use fruit flies as the basis of affordable, meaningful research projects for people who are at this stage in their academic careers. That should enable us to create a biomedical research community that doesn’t really exist at the moment.”

̽��ֱ��inspiration for DrosAfrica came from workshops organised in 2011 by Lucia Prieto Godino, at the ̽��ֱ�� of Cambridge, and the Nigerian scientist, Professor Sadiq Yusuf at Kampala International ̽��ֱ��, Uganda, at which Palacios and others taught. These set out to equip scientists and faculty members with the knowledge and skills needed to undertake research in biomedical science and state-of-the-art cellular biology using fruit flies. Although DrosAfrica is an independent initiative, Palacios continues to collaborate with Godino. More workshops are now being planned in Kenya and Nigeria for 2016.

Participants are given guidance on how to set up their own research project to study topics such as cancer, the immune system, or infectious diseases. ̽��ֱ��workshops also provide opportunities to network with other researchers from across Africa who share similar interests, and allocate each participant a mentor who helps them further develop their own ideas and experiments. An online learning community has also been established, to promote interaction between alumni and the sharing of resources and information.

̽��ֱ��workshops have also now led to the establishment of new laboratories in various African Universities undertaking fruit fly research. According to a follow-up survey conducted by the DrosAfrica group, labs have been set up at the ̽��ֱ�� of Nairobi in Kenya, focusing on host-pathogen interactions in various diseases; and at Kampala International ̽��ֱ�� in Uganda, where MSc and PhD students are learning to use Drosophila in teams carrying out research on subjects such as antimalarial drugs, depression, epilepsy, and the role of nutrition in controlling stress.

A project to establish a Drosophila unit at the International College of Health Sciences and Liberal Arts, Nigeria, by one of the senior DrosAfrica alumni, is also being supported by the group.

In addition to doing research, these centres are planning to run their own workshops in the near future, which Dr Palacios hopes will enable the initiative to spread to other African institutions. She likens the model to that of Spain where, 40 years ago, top scientific research labs were few and far between. Almost by chance one lab started working on Drosophila and there are now several dozen of research centres – including some of the best Drosophila labs anywhere in the world – training emerging Spanish scientists.

“What we would really like to achieve, and what we are now beginning to get, is a situation where researchers are setting up their own labs and running ambitious experiments without having to leave Africa itself,” she said. “ ̽��ֱ��work that they are undertaking has the potential to have a real impact on human welfare.”

̽��ֱ��DrosAfrica project involves academics from the Universities of Cambridge, Bristol and Bath in the UK, the ̽��ֱ�� Pablo Olavide in Spain, and the Instituto Gulbenkian de Cicencia in Portugal, and Kampala International ̽��ֱ�� in Uganda. ̽��ֱ��project is supported by the Cambridge-Africa Programme and the Alborada Fund. Further information about the DrosAfrica project can be found at: http://drosafrica.org/.

Fruit flies are proving the unlikely source of a new initiative to help improve postgraduate research opportunities in Africa, with the support of Cambridge academics.

Students at African universities who start a PhD often find that they can’t really do much research and end up lecturing and teaching instead. Our big idea is to use fruit flies as the basis of affordable, meaningful research projects for people who are at this stage in their academic careers.

Isabel Palacios

Drosophila melanogaster

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Scientists wake up to causes of sleep disruption in Alzheimer’s disease

fpjl2 — Thu, 27 Feb 2014 10:10:58 +0000

Being awake at night and dozing during the day can be a distressing early symptom of Alzheimer's disease, but how the disease disrupts our biological clocks to cause these symptoms has remained elusive.

Now, scientists from Cambridge have discovered that in fruit flies with Alzheimer's the biological clock is still ticking but has become uncoupled from the sleep-wake cycle it usually regulates. ̽��ֱ��findings – published in Disease Models & Mechanisms – could help develop more effective ways to improve sleep patterns in people with the disease.

People with Alzheimer's often have poor biological rhythms, something that is a burden for both patients and their carers. Periods of sleep become shorter and more fragmented, resulting in periods of wakefulness at night and snoozing during the day. They can also become restless and agitated in the late afternoon and early evening, something known as 'sundowning'.

Biological clocks go hand in hand with life, and are found in everything from single celled organisms to fruit flies and humans. They are vital because they allow organisms to synchronise their biology to the day-night changes in their environments.

Until now, however, it has been unclear how Alzheimer's disrupts the biological clock. According to Dr Damian Crowther of Cambridge's Department of Genetics, one of the study's authors: "We wanted to know whether people with Alzheimer's disease have a poor behavioural rhythm because they have a clock that's stopped ticking or they have stopped responding to the clock."

̽��ֱ��team worked with fruit flies – a key species for studying Alzheimer's. Evidence suggests that the A-beta peptide, a protein, is behind at least the initial stages of the disease in humans. This has been replicated in fruit flies by introducing the human gene that produces this peptide.

Taking a group of healthy flies and a group with this feature of Alzheimer's, the researchers studied sleep-wake patterns in the flies, and how well their biological clocks were working.

They measured sleep-wake patterns by fitting a small infrared beam, similar to movement sensors in burglar alarms, to the glass tubes housing the flies. When the flies were awake and moving, they broke the beam and these breaks in the beam were counted and recorded.

To study the flies' biological clocks, the researchers attached the protein luciferase – an enzyme that emits light – to one of the proteins that forms part of the biological clock. Levels of the protein rise and fall during the night and day, and the glowing protein provided a way of tracing the flies' internal clock.

"This lets us see the brain glowing brighter at night and less during the day, and that's the biological clock shown as a glowing brain. It's beautiful to be able to study first hand in the same organism the molecular working of the clock and the corresponding behaviours," Dr Crowther said.

They found that healthy flies were active during the day and slept at night, whereas those with Alzheimer's sleep and wake randomly. Crucially, however, the diurnal patterns of the luciferase-tagged protein were the same in both healthy and diseased flies, showing that the biological clock still ticks in flies with Alzheimer's.

"Until now, the prevailing view was that Alzheimer's destroyed the biological clock," said Crowther.

"What we have shown in flies with Alzheimer's is that the clock is still ticking but is being ignored by other parts of the brain and body that govern behaviour. If we can understand this, it could help us develop new therapies to tackle sleep disturbances in people with Alzheimer's."

Dr Simon Ridley, Head of Research at Alzheimer's Research UK, who helped to fund the study, said: "Understanding the biology behind distressing symptoms like sleep problems is important to guide the development of new approaches to manage or treat them. This study sheds more light on the how features of Alzheimer's can affect the molecular mechanisms controlling sleep-wake cycles in flies.

"We hope these results can guide further studies in people to ensure that progress is made for the half a million people in the UK with the disease."

New research using fruit flies with Alzheimer’s protein finds that the disease doesn’t stop the biological clock ticking, but detaches it from the sleep-wake cycle that it usually regulates. Findings could lead to more effective ways to improve sleep patterns in those with Alzheimer’s.

We have shown in flies with Alzheimer's that the clock is still ticking but being ignored by other parts of the brain

Damian Crowther

Dr. Stanislav Ott

̽��ֱ��fly brain is half a millimeter across and contains approximately 100,000 nerve cells (green). ̽��ֱ��A-beta peptide forms plaques (red) that are linked to nerve cell death and behavioral abnormalities in the flies.

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World first for fly research

ljm67 — Fri, 15 Feb 2013 14:15:15 +0000

̽��ֱ��first ever basic training package to teach students and scientists how to best use the fruit fly, Drosophila, for research has been published. It’s hoped it will encourage more researchers working on a range of conditions from cancer to Alzheimer’s disease to use the humble fly.

̽��ֱ��unique scheme has been put together by Dr Andreas Prokop from the Faculty of Life Sciences at the ̽��ֱ�� of Manchester and John Roote from the Department of Genetics at the ̽��ֱ�� of Cambridge.

John Roote said, “In 1910 Thomas Hunt Morgan isolated the first Drosophila sex-linked mutation, white. Since then many thousands of research workers have realised the potential of the humble fruit fly.

“ ̽��ֱ��powerful research tools that we have today combined with a century of background knowledge, the vast collections of stocks that are available to everyone and the fortuitous ‘pre-adaptation’ of the fly for life in a laboratory ensure that Drosophila melanogaster maintains its position as the pre-eminent model organism for research in genetics. However, until now a comprehensive teaching programme to guide students through the often daunting first few steps has been surprisingly absent.”

Dr Prokop said: “People don’t realise just how useful the tiny fruit fly can be when it comes to research. Fellow scientists are often not aware of their genetic value for research. For example, about 75% of known human disease genes have a recognisable match in the genome of fruit flies which means they can be used to study the fundamental biology behind complex conditions such as epilepsy or neurodegeneration.”

Fruit flies have been used for scientific research for more than a hundred years. They have allowed scientific breakthroughs in genetics, body structure and function. ̽��ֱ��first jet lag gene and the first learning gene were identified in flies as well as breakthroughs in neuroscience, such as the discovery of the first channel proteins.

Dr Prokop says: “Flies need very little space so are ideal for breeding. They develop in just two weeks and it is a simple process to follow a genetic mutation through the generations by analysing the patterns on their bristles, wings or eyes which provide easy visible markers.”

Despite the flies’ contribution to scientific research through the ages, including four Nobel prizes, there is a concern that fewer scientists are aware of their potential. Part of the reason for this has been a trend away from basic genetics training in schools and universities which makes it harder for newcomers to the fly.

Together with John Roote, the manager of the main Cambridge fly facility, Dr Prokop has developed a four part training package for all scientists. It includes a self-study introductory manual, a short practical session on gender and marker selection, an interactive Powerpoint presentation and finally an independent training exercise in mating scheme design.

Dr Prokop says it’s a well rounded package: “We wanted to make sure that key aspects of fly research become apparent to the newcomer right away, such as a basic appreciation of why Drosophila is used for research, the nature of the fly stocks we use, an understanding of classical genetic rules and the knowledge of the nature and use of classical genetic markers but also the use of modern transgenic technologies.”

He continues: “We’ve had a really good response from people who’ve tested the training package and we’re confident this will encourage more scientists to consider using the fruit fly in the future.”

To access the training package, you can go to the following link: http://figshare.com/articles/How_to_design_a_genetic_mating_scheme_a_bas...

A paper outlining the package has been published in the February edition of the journal G3.

Story adapted from ̽��ֱ�� of Manchester press release.

A how-to manual for fruit fly research has been created.

Until now a comprehensive teaching programme to guide students through the often daunting first few steps has been surprisingly absent

John Roote

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Surprising solution to fly eye mystery

gm349 — Thu, 11 Oct 2012 19:00:27 +0000

Fly eyes have the fastest visual responses in the animal kingdom, but how they achieve this has long been an enigma. A new study shows that their rapid vision may be a result of their photoreceptors - specialised cells found in the retina - physically contracting in response to light. ̽��ֱ��mechanical force then generates electrical responses that are sent to the brain much faster than, for example, in our own eyes, where responses are generated using traditional chemical messengers. ̽��ֱ��study was published today, in the journal Science.

It had been thought that the ion channels responsible for generating the photoreceptors’ electrical response were activated by chemical messengers as is usually the case in cell signalling pathways. However, these results suggest that the light-sensitive ion channels responsible for the photoreceptor’s electrical response may be physically activated by the contractions – a surprising solution to the mystery of light perception in the fly’s eye and a new concept in cellular signalling.

Professor Roger Hardie, lead author of the study from the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience, said: “ ̽��ֱ��ion channel in question is the so-called ‘transient receptor potential’ (TRP) channel, which we originally identified as the light-sensitive channel in the fly in the 1990’s. It is now recognised as the founding member of one of the largest ion channel families in the genome, with closely related channels playing vital roles throughout our own bodies. As such, TRP channels are increasingly regarded as potential therapeutic targets for numerous pathological conditions, including pain, hypertension, cardiac and pulmonary disease, cancer, rheumatoid arthritis, and cerebral ischaemia. We are therefore hopeful that these new results may have significance well beyond the humble eye of the fly.”

A fly’s vision is so fast that it is capable of tracking movements up to five times faster than our own eyes. This performance is achieved using microvillar photoreceptor cells, in which the photo-receptive membrane is made up of tiny tubular membranous protrusions known as microvilli. In each photoreceptor cell, tens of thousands of these are packed together to form a long rod-like structure, which acts as a light-guide to absorb the incident light. Each microvillus also houses the biochemical machinery, which converts the energy of the absorbed light into the electrical responses that are sent to the brain – a process known as phototransduction.

As in all photoreceptors, phototransduction starts with absorption of light by a visual pigment molecule (rhodopsin). In microvillar photoreceptors this leads to activation of a specific enzyme known as phospholipase C (PLC). PLC is a ubiquitous and very well-studied enzyme, which cleaves a large piece from a specific lipid component of the cell membrane (“PIP₂”), leaving a smaller membrane lipid (DAG) in its place.

Somehow this enzymatic reaction leads to the opening of “ion channels” in the microvillus membrane; once opened, these allow positively charged ions such as Ca²⁺ and Na⁺ to flow into the cell thus generating the electrical response. This basic sequence of events has been established for over 20 years; but exactly how PLC’s enzymatic activity causes the opening of the channels has long remained a mystery and one of the major outstanding questions in sensory biology.

Professor Hardie added: “ ̽��ֱ��conventional wisdom would be that one of the products of this enzyme’s activity is a chemical ‘second messenger’ that binds to and activates the channel. However, years of research had previously failed to find compelling evidence for such a straightforward mechanism.”

̽��ֱ��new study, which was funded by the BBSRC and the Medical Research Council, using the fruitfly, Drosophila, now suggests a remarkable and unexpected resolution to this mystery. ̽��ֱ��key finding was that the photoreceptors physically contract in response to light flashes. ̽��ֱ��contractions were so small and fast that an “atomic force microscope” was needed to measure them. This revealed that the contractions were even faster than the cell’s electrical response and appeared to be caused directly by PLC activity.

̽��ֱ��researchers believe that the splitting of the membrane lipid PIP₂ by the enzyme PLC reduces the membrane area, thereby increasing tension in the membrane and causing each tiny microvillus to contract in response to light. ̽��ֱ��synchronised contraction of thousands of microvilli together then accounts for the contractions measured from the whole cell.

Dr Kristian Franze, co-author of the paper from the ̽��ֱ�� of Cambridge, said: “We propose that within each microvillus the increase in membrane tension acts directly on the light-sensitive channels. In other words, rather than using a traditional chemical 2^nd messenger, the channels were being activated mechanically.”

This concept was supported by experiments in which the native light-sensitive channels were eliminated by mutation and replaced with mechano-sensitive channels, which are known to open in response to membrane tension. Remarkably, these photoreceptors still generated electrical signals in response to light, but were now mediated by activation of the ectopic mechano-sensitive channels. To test whether the native light-sensitive channels could be affected by mechanical forces in the membrane, the microvillar membrane was stretched or compressed by changing the osmotic pressure. This simple experimental manipulation rapidly enhanced or suppressed channel openings in response to light as predicted.

These results suggest that PLC mediates its effects in the photoreceptors by changing the mechanical state of the membrane. ̽��ֱ��researchers suggest that it is the increase in the membrane tension (along with a pH change also resulting from PLC activity) that triggers the opening of the light-sensitive channels. Mechano-sensitive ion channels are actually well known, but normally involved in transducing mechanical stimuli – such as sound in the ears or pressure on the skin. One of their characteristics is that they can be activated extremely rapidly – perhaps an explanation for why fly photoreceptors have evolved this solution to phototransduction.

Professor Hardie said: “That a mechanical signal could be an intermediate signal -or ‘second messenger’- in an otherwise purely biochemical cascade is a novel concept that extends our understanding of cellular signalling mechanisms to a new level.”

For more information, please contact Genevieve Maul (genevieve.maul@admin.cam.ac.uk) at the ̽��ֱ�� of Cambridge Office of External Affairs and Communications.

Research provides insight into why flies have the fastest vision in the animal kingdom.

̽��ֱ��conventional wisdom would be that one of the products of this enzyme’s activity is a chemical ‘second messenger’ that binds to and activates the channel. However, years of research had previously failed to find compelling evidence for such a straightforward mechanism.

Professor Roger Hardie, lead author of the study from the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience

Image H. Meinecke

Blowfly

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