NMR, Kidneys and a Family

Alu_MaricaCutajrr

I chose to study Chemistry and Physics simply because they were the subjects I enjoyed most, so I enrolled on a B.Sc. (Hons) degree at the University of Malta without having a clear idea about what I would be doing once the four years are over. I was not the best brain in the class but in 2004 I graduated with a 2:1 grade and it was quite obvious that I needed a plan. A couple of opportunities to embark on a Ph.D. in Britain came along through local contacts and applications on jobs websites. Despite not knowing much about the subject, I decided to go with the Ph.D. at Exeter University because it was about Nuclear Magnetic Resonance, a subject that sits right on the verge of Chemistry and Physics.

Obviously the idea of moving abroad, living away from my parents and starting this amazing new adventure was incredibly exciting. From the start of my Ph.D. things went incredibly well, it was immediately obvious that I was much better at doing research than studying for exams. I started with looking into dynamics in solid materials on the microsecond timescale, which is the less studied type of motion. It bridges the gap between very fast (spin-lattice relaxation motions, nanosecond) and slow (millisecond to second) timescales. I published my first scientific paper a year into my Ph.D., and five more followed by the time I defended my thesis.

Because of the contacts I built during my Ph.D. as soon as I finished I was offered a post at University College London, Institute of Child Health, working as a research fellow in renal imaging. I carry out research at Great Ormond Street Children’s Hospital using novel non-invasive Magnetic Resonance Imaging (MRI) techniques. I work mainly with children requiring a kidney transplant. The aim of my work is to eventually be able to furnish doctors with information about their patients, which is currently either unavailable to them or they can only get through invasive clinical techniques such as biopsies. My work here has produced six peer-reviewed papers and I am currently working on a few more.

The research I carried out during my Ph.D. involved dealing with basic scientific concepts like Quantum Mechanics — that studies sub-atomic phenomena — and I was at liberty to experiment as I saw fit, which I enjoyed. However, despite being much more restrictive, I find clinical research extremely rewarding. Coming face to face with the people benefiting from all your hard work is really priceless.

Just after my Ph.D. I married my husband. We are now very proud parents of a two-year-old son. Any working mum would tell you that raising a family while maintaining a career is not easy, but I believe that if you like your job enough, combing the two is very worthwhile. Obviously research does not wait for anyone, and luckily for me, having colleagues that supported me meant that I was able to carry on publishing while I was on maternity leave.

Getting the Rhythm

Music has changed society. Stephanie Mifsud met ethnomusicologist Dr Philip Ciantar to talk about music from all over the world. Studying diverse musical traditions has taught him about himself and how music can bridge cultural divides to bring us together

Classical, romantic, baroque, rock, hip hop… music continues to change throughout the years, yet we all look for that beat that gets us moving. How can we not when music is such an important part of our life?

Music is found everywhere: on television adverts, films, on the radio and at places of worship. Our society immerses us in it for hours every day. A person will listen to music that represents the way they feel. Music has the potential to influence moods, feelings, and thoughts.

“Music opens infinite thinking modes unknown to us and uncovers situations we wouldn’t otherwise experience”

Legendary rock guitarist Jimi Hendrix, told Life magazine in 1969, ‘I can explain everything better through music. You hypnotise people to where they go right back to their natural state, and when you get people at their weakest point, you can preach into their subconscious what we want to say.’

Music, like language, has a common factor: a person’s active role. People create music. No music can exist without the people who make it.

The Ethnomusicologist Dr Philip Ciantar (University of Malta) is interested in both the music itself, as a humanly organised sound, and the musicians. His research focuses on understanding how people worldwide think about music and how that affects their music. He meets and interviews countless musicians and their audiences. People’s thinking about music is shaped by who they are, their world-view, and how they use their creative imagination to create music. Take John Lennon’s song Imagine. The song has touched countless around the world. It might have changed the way people see themselves, relate to the people around them, and influenced future songs.

Dr Philip Ciantar
Dr Philip Ciantar

Music to say ‘Hello!’

Ciantar explains that ‘by listening to and exploring music from different countries we can understand other cultural and social realities. Music opens infinite thinking modes unknown to us and uncovers situations we wouldn’t otherwise experience.’ According to him, ‘music can highlight social issues or it can make a connection with different cultures when many other avenues fail’. This is the acceptance of ‘otherness’, the concept of what makes us different from each other culturally and socially. Music can be a very effective medium.

Acceptance of different cultures needs to be taught from a young age. Music can help in showing people the advantages of multiculturalism. Ciantar suggests that, at school, children can be taught instruments used in different cultures. This would help students understand and appreciate not just the instruments but also the musicians playing them. He continues, ‘you need to be open to other opinions, cultures, and traditions’ and music provides the right scenario.

Understanding music globally should lead to appreciation of diverse sounds and how they are made, communicated, and transformed into meaning. The musical process reveals humanity and here otherness surfaces as a challenge for us to deal with. It is up to us to then connect with different cultures we might consider alien.

People come together through music. The village feast is Malta’s best example of unity through music. During a feast a quiet pjazza transforms into a music concert, a fireworks festival, and a food extravaganza — uniting the whole community. These celebrations bring people together ignoring their differences.

Multiculturalism is a worldwide phenomenon. Malta is becoming multicultural and, as Ciantar comments, ‘music is an indicator of what is going on. Performances of African music at the Marsa Open Centre can be interpreted as a plea for social acceptance and cultural integration. Slavic street players in Republic Street play Bach’s violin partitas to make us connect with them culturally. Once we are connected they play a nostalgic lullaby from their homeland to make us feel the pain of distance and sympathise with them. Undoubtedly, music serves as a social text; in itself, an intriguing sonic document that links the evident with the untold or even ignored.’ This is the power of music and the concept of otherness that can shape our thoughts on multiculturalism and readiness to accept others’ views.

“Undoubtedly, music serves as a social text; in itself, an intriguing sonic document that links the evident with the untold or even ignored”

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He became even more aware of multiculturalism while conducting his Ph.D. research. He went to Libya to experience different cultural backgrounds and traditions. He worked with Libyan musicians, attending their rehearsals, talked to people on Tripoli’s streets about the musical tradition of ma’lūf (a tradition valued for its Andalusian legacy), and sneaked in percussion performances with Libyan musicians. Apart from writing a book, these experiences helped Ciantar understand otherness and the challenges it implies.

Ciantar’s first experience with ethnomusicology and otherness goes back to 1991, when he was inspired by the writings of John Blacking and Bruno Nettl, and started researching Maltese folk music għana. He saw how the għanejja performed in two different contexts and their music changed accordingly. The music they sang was more elaborate in their regular bars when compared to stage music with an unknown audience.

Otherness can also be scrutinised through musical translation. Ciantar researches musical translation: how we digest and eventually accept music that might not be initially appealing to us. Recently, he composed a Maltese festa band march out of tunes that he had recorded in Libya. The process allowed him to investigate the music and himself. He had to take elements of one musical tradition and apply it to another that was culturally remote, using himself to understand the process of how a person thinks and transforms thought into music.

Ciantar is very hopeful of the musical evolution in Malta as this is being influenced by the different cultures that people encounter everyday. This will create a more varied musical scene. Ciantar can already feel the difference.

 

Stephanie Mifsud is part of the Department of English Master of Arts programme.

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Find out more:

John Lennon’s Imagine

Andalusian Music

Għana Maltija—Traditional Maltese music

Forgetting what you can’t remember

Giuliabugeja
How does the loss of memory change a person? Can media replace memory?  Giulia Bugeja asks several researchers to find out the affect on cultural memory and she also touches on dementia

When Mike* went to the nursing home that evening to visit his grandmother Maria*, she was worried that he wouldn’t be able to find her because the caretakers had changed her room. Mike tried explaining to her that her room on the 4th floor had been refurbished a year ago, but she couldn’t remember.

Dr James Corby
Dr James Corby

‘Can life without memory be considered a meaningful existence?’ asks Dr Charles Scerri (Malta Dementia Society, and Department of Pathology, University of Malta). Dr Scerri researches dementia. He is currently examining which physical environments and what sort of psychosocial wellbeing can improve life in local dementia hospital wards. In fact, Dr Scerri reports that today there are over 44 million people suffering from some form of dementia. That is around 100 times the Maltese population. He asks, ‘what type of society can we end up with if we are wholly made up of individuals with no past and an uncertain future?’

With more people relying on new media technology to record information and experiences, Dr Scerri’s question faces a future society where media could replace memory. ‘It would be short-sighted to think that new media will have no long-term influence on the complex nexus of personal and cultural memory’, says Dr James Corby (Department of English, UoM).

Photography already acts as a surrogate for memory. But, it does not stop there; theorist Roland Barthes goes one step further saying how photography can capture details missed by the human eye. As developers of new media strive to enhance experiences, more users are adopting them. In the final quarter of 2012 alone, Apple sold 37.4 million iPhones. This smartphone, equipped with HD video, an in-built camera, calendar, and interactive 3D map helps people capture memories and avoid having to remember appointments or directions. It even comes with Siri, your own ‘personal assistant’, to use Apple’s words.

Despite these abilities, Dr Corby is sceptical. As a researcher working on the interfaces between literature, philosophy and culture, Dr Corby thinks that the rich tradition of the humanities should inform debates about cultural memory. ‘The idea that a facility to record memories leads to the diminishment of personal memory is by no means a new idea. Indeed, it is precisely the accusation that, in Plato’s Phaedrus, Socrates makes against writing.’ Writing did not steal our ability to remember and neither should new technologies.

“You can never really know if what she’s saying is true because her memories are not always real”

So what would happen if old or new media failed us? When the accounts office of the family business burned down, Mike could relate to his grandmother’s anxiety due to her lack of personal memory. All the accounting records, invoices, transaction records, and overseas payments were destroyed. The accountant was so shocked that he still will not enter his old office after 15 years.

The accountant had to keep paper records. There was too much information to remember and they couldn’t memorise it all. Although they recorded the information they still lost it in the fire.

More about Alzheimer’s in Malta
The Hon Mario Galea, Parliamentary Secretary for the Elderly and Community Care, will launch the book X'Hin hu? co-authored by Charles Scerri and Trevor Zahra. The publication focuses on dementia and is aimed for the general public.   Elders who experienced or worked n the field of dementia will share their experiences.   Juventutis Domus, 63, Triq San Girgor, ZejtunDr Scerri has collaborated with the Department of Pathology to launch the Alzheimer’s Disease Research Group (University of Malta). Their objective is to gather several multidisciplinary professionals to ‘promote and facilitate research and scientific collaboration in Alzheimer’s disease and other forms of dementia’. Together with Trevor Zahra, he recently released the publication X’ħin hu? Fatti dwar id-dimensja (What time is it? Facts about dementia).

We all risk losing both valuable information and the recollection of experiences. So what would happen if Malta became a nation of people without a memory of important events? For Dr Corby, a society which relies on new media and less on memory ‘might then lead to a complete eliding of any difference between personal memory and an increasingly undifferentiated surfeit of readily available cultural memory — a sort of technologised and globalised cultural eidetic memory’.

There’s also the possibility that media such as photographs could lead to the creation of cultural memories which never took place. ‘I imagine false memory to be the norm—it would be naïve to think that the visual representation of a culture […] is free from ideology’ says Dr Corby. Our national identity will instead be formed around uncertain events.

Joe Rosenthal’s photograph of American soldiers raising the American flag on Mount Suribachi on the island of Iwo Jima signifies a moment of national pride for Americans. Few Americans are aware that the photograph shows the flag being raised for a second time. The first flag was too small but the second larger flag would be seen by incoming ships.

Similarly, on the 4th floor of a nursing home, an old woman recalls how the nurses refused to take down the Christmas decorations. In her room, there was only a lone poppy. ‘She often creates stories in her head’, says Mike. ‘You can never really know if what she’s saying is true because her memories are not always real.’

‘Memories are created by altering a set of connections between brain cells so that one cell stimulates the others,’ says Jonah Lehrer, Wired Magazine. By creating memories, we are literally rewiring our brains. Every time a memory is recalled, the connection between brain cells is restructured and the memory altered depending on the stimuli of the current situation. This means that whilst media may fail us, so might our memories.

Will a nation inevitably make the same mistakes because its people cannot remember past experiences or because they replace them with false ones? When asked how memory recall can be assisted, Dr Scerri acknowledges that media is a useful tool in improving memory, as ‘memory albums are extremely valuable for individuals with dementia in facilitating memory events and in reducing anxiety and confusion’. Perhaps these tools can help Mike’s grandmother.

 

*Names have been changed to protect the identity of the people mentioned in the article.

Giulia Bugeja is part of the Department of English Master of Arts programme.

Look out for an in-depth feature on dementia in the next issue.

Stalking E.T.

AlessioMagro
There are over 100 billion galaxies in our universe. Each galaxy has billions of stars. Each star could have a planet. Planets can breathe life. Alessio Magro writes about his experience hunting for E.T. Illustrations by Sonya Hallett

 

In 1982, 4 years before I was born, the world fell in love with Spielberg’s E.T. the Extra-Terrestrial. Fifteen years later, the movie Contact, an adaptation of Carl Sagan’s novel, hit the big screen. Although at the time I was too young to appreciate the scientific, political, and religious themes I was captivated and it fired my thoughts. I questioned whether we are alone in this vast space. What would happen if E.T. does call? Are we even listening? If so, how? And, is it all a waste of time and precious money? Instead of deflating me, these questions inspired me to start a journey that led me to my collaboration with SETI, the Search for Extra Terrestrial Intelligence. I participated in ongoing efforts to try and find intelligent civilisations on other worlds.

The debate on whether we are alone started ages ago. It was first debated in Thales,  Ancient Greece. Only recently has advanced technology allowed us to try and open up communication channels with any existing advanced extraterrestrial civilisations. If we do not try we will never answer this question.

For the past fifty years we have been scanning the skies using large radio telescopes and listening for signals which cannot be generated naturally. The main assumption is that any advanced civilisation will follow a similar technological path as we did. For example, they will stumble upon radio communication as one of the first wireless technologies.

SETI searches are usually in the radio band. Large telescopes continuously scan and monitor vast patches of the sky. Radio emissions from natural sources are generally broadband, encompassing a vast stretch of the electromagnetic spectrum — waves from visible light to microwaves and X-rays — whilst virtually all human radio communication has a very narrow bandwidth, making it easy to distinguish between natural and artificial signals. Most SETI searches therefore focus on searching for narrow band signals of extraterrestrial origin.

Narrow bands are locked down by analysing a telescope’s observing band — the frequency range it can detect. This frequency range is broken down into millions or billions of narrow frequency channels. Every channel is searched at the same time. SETI searches for sharp peaks in these small channels. This requires a large amount of computational resources, such as supercomputing clusters, specialised hardware systems, or through millions of desktop computers. The infamous SETI@home screen-saver extracted computer power from desktops signed up to the programme, which started as the millennium turned.

E.T. civilisations might also transmit signals in powerful broadband pulses. This means that SETI could search for wider signal frequencies. However, they are more difficult to tease apart from natural emissions, so they require more thorough analysis. The problem is that as broadband signals — natural or otherwise — travel through interstellar space they get dispersed, resulting in higher frequencies arriving at the telescope before lower ones, even though they both were emitted at the same time. The amount of dispersion, the dispersion gradient, depends on the distance between the transmitter and receiver. The signal can only be searched after this effect is accounted for by a process called dedispersion. To detect E.T. signs, thousands of gradients have to be processed to try out all possible distances. This process is nearly identical to that used to search for pulsars, which are very dense, rapidly rotating stars emitting a highly energetic beam at its magnetic poles. Pulsars appear like lighthouses on telescopes, with a regular pulse across the entire observation band.

For the past four years I have been developing a specialised system which can perform all this processing in real-time, meaning that any interesting signals will be detected immediately. Researchers now do not need to wait for vast computers to process the data. This reduces the amount of disk space needed to store it all. It also allows observations to be made instantaneously, hence reducing the risk of losing any non-periodic, short duration signals. To tackle the large computational requirements I used Graphics Processing Units (GPUs) — typically unleashed to work on video game graphic simulations — because a single device can perform tasks of at least 10 laptops. This system can be used to study pulsars, search for big explosions across the universe, search for gravitational waves, and for stalking E.T..

The Electromagnetic Spectrum. Higher frequencies mean higher energies but shorter wavelengths. X-rays and Gamma rays are on the higher end of the spectrum making them so dangerous.
The Electromagnetic Spectrum. Higher frequencies mean higher energies but shorter wavelengths. X-rays and Gamma rays are on the higher end of the spectrum making them so dangerous.

E.T. we love you

Hunting for planets orbiting other stars, known as exoplanets, has recently become a major scientific endeavour. Over 3,500 planet-candidates were found by the Kepler telescope that circles our planet, about 961 are confirmed. Finding so many planets is now leading scientists to believe that the galaxy is chock-full of them. The current estimate: 100 billion in our galaxy, with at least one planet per star. For us E.T. stalkers, this is music to our ears.

Life could be considered inevitable. However, not all planets can harbour life, or at least life as we know it. Humans need liquid water and a protective atmosphere, amongst other things. Life-supporting planets need to be approximately Earth-sized and orbit within its parent star’s habitable zone. This Goldilocks zone is not too far away from the sun, freezing the planet, or too close to it, frying it. These exoplanets are targeted by SETI searches, which perform long duration observations of exoplanets similar to Earth.

“The big question is: where do we look for E.T.? I would prefer rephrasing to: at which frequency do we listen for E.T.?”

By focusing on these planets, SETI is gambling. They are missing huge portions of the sky to focus on areas that could yield empty blanks. SETI could instead perform wide-field surveys which search large chunks of the sky for any interesting signals. Recent development in radio telescope technology allows for the instantaneous observation of the entire sky, making 24/7 SETI monitoring systems possible. Wide-field surveys lack the resolution needed to figure out where a signal would come from, so follow-up observations are required. Anyhow, a one-off signal would never be convincing.

For radio SETI searches, the big question is: where do we look for E.T.? I would prefer rephrasing to: at which frequency do we listen for E.T.? Imagine being stuck in traffic and you are searching for a good radio station without having a specific one in mind. Now imagine having trillions of channels to choose from and only one having good reception. One would probably give up, or go insane. Narrowing down the range of frequencies at which to search is one of the biggest challenges for SETI researchers.

The Universe is full of background noise from naturally occurring phenomena, much like the hiss between radio stations. Searching for artificial signals is like looking for a drop of oil in the Pacific Ocean. Fortunately, there exists a ‘window’ in the radio spectrum with a sharp noise drop, affectionately called the ‘water hole’. SETI researchers search here, reasoning that E.T. would know about this and deliberately broadcast there. Obviously, this is just guesswork and some searches use a much wider frequency range.

Two years ago we decided to perform a SETI survey. Using the Green Bank Telescope in West Virginia (USA), the world’s largest fully steerable radio dish, we scanned the same area the Kepler telescope was observing whilst searching for exoplanets. This area was partitioned into about 90 chunks, each of which was observed for some time. In these areas, we also targeted 86 star systems with Earth-sized planets. We then processed around 3,000 DVDs worth of data to try and find signs of intelligent life. We developed the system ourselves at the University of Malta, but we came out empty handed.

 

 

A camera shy E.T.

Should we give up? Is it the right investment in energy and resources? These questions have plagued SETI from the start. Till now there is no sign of E.T., but we have made some amazing discoveries while trying to find out.

Radio waves were discovered and entered into mainstream use in the late 19th century. We would be invisible to other civilisations unless they are up to 100 light years away. Light (such as radio) travels just under 9.5 trillion kilometres per year. Signals from Earth have only travelled 100 light years, broadcasts would take 75,000 years to reach the other side of our galaxy. To compound the problem, technology advances might soon make most radio signals obsolete. Taking our own example, aliens would have a very small time window to detect earthlings. The same reasoning works the other way, E.T. might be using technologies which are too advanced for us to detect. As the author Arthur C. Clarke stated, ‘any sufficiently advanced technology is indistinguishable from magic’.

The Wow! signal is a brief, strong radio burst of unknown origin detected by the Big Ear Telescope, SETI search, 1977. If it originated from deep space, it could either be a new astrophysical phenomena or an alien signal.
The Wow! signal is a brief, strong radio burst of unknown origin detected by the Big Ear Telescope, SETI search, 1977. If it originated from deep space, it could either be a new astrophysical phenomena or an alien signal.

At the end of the day, it is all a probability game, and it is a tough one to play.  Frank Drake and Carl Sagan both tried. They came up with a number of factors that influence the chance of  two civilisations communicating. One is that we live in a very old universe, over 13 billion years old, and for communication between civilisations their time windows need to overlap. Another factor is, if we try to detect other technological signatures they might also be obsolete for advanced alien life. Add to these parts, the assumed number of planets in the Universe and the probability of an intelligent species evolving. For each factor, several estimates have been calculated. New astrophysical, planetary, and biological discoveries keep fiddling with the numbers that range from pessimistic to a universe teeming with life.

The problem with a life-bloated galaxy is that we have not found it. Aliens have not contacted us, despite what conspiracy theorists say. There is a fatalistic opinion that intelligent life is destined to destroy itself, while a simpler solution could be that we are just too damned far apart. The Universe is a massive place. Some human tribes have only been discovered in the last century, and by SETI standards they have been living next door the whole time. The Earth is a grain of sand in the cosmic ocean, and we have not even fully explored it yet.

“Signals from Earth have only travelled 100 light years, broadcasts would take 75,000 years to reach the other side of our galaxy”

Still, the lack of alien chatter is troubling. Theorists have come up with countless ideas to explain the lack of evidence for intelligent alien existence. The only way to solve the problem is to keep searching with an open mind. Future radio telescopes, such as the Square Kilometre Array (SKA), will allow us to scan the entire sky continuously. They require advanced systems to tackle the data deluge. I am part of a team working on the SKA and I will do my best to make this array possible. We will be stalking E.T. using our most advanced cameras, and hopefully we will catch him on tape.

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Carl Sagan’s Cosmos

Exoplanets Galore

Do we live our wishes when dreaming?

Made infamous by Sigmund Freud, the idea is that we spend one third of our lives dreaming about what we would like to do. Our rational brain suppresses these feelings.

On the other extreme, our brain is just as active in certain sleep stages. These neural firings express themselves in dreams. There are no deep hidden emotions behind them.

Somewhere in between lie recent studies that show that dreams are important in memory, learning and emotions. If you sleep without dreaming these qualities will suffer. For example, rat studies in 2001 showed how while dreaming they replayed solutions to mazes to commit them to their long-term memory.

 

Send your questions to think@um.edu.mt and we’ll find out if it’s the truth or just a fib!

Flying in the face of Neurodegeneration

RubenCauchi
Fruit flies are not human. Yet they are close enough to have been used for over 100 years by scientists to find out more about humans. Dr Ruben J. Cauchi writes about his relationship with the fly. He uses it to find out how to stop Alzheimer’s disease, Parkinson’s disease, and Motor Neuron Disease that affect tens of millions

It was a cold and grey February afternoon. Snowflakes were pelting the dreaming spires of Oxford. This gloomy weather did nothing to impede the warmth and buzz exuding from the laboratories crammed in the iconic Sherrington building. Less than a century earlier, this labyrinthine edifice was the habitat of Sir Charles Sherrington whose experiments shaped our understanding of the ‘synapse’ or the minute gaps between one brain cell (neuron) and another. The Sherrington building (part of the Department of Physiology, Anatomy, and Genetics at Oxford University) has undergone several expansions over the years. In its newest wing, nowadays it houses the research group of Dr Ji-Long Liu, a rising star in the field of genetics and cell biology.

For me, this was no ordinary afternoon. Together with Liu’s lab teammates, I was perched on a stereomicroscope whilst holding a delicate brush in my hands. On one side was a tray jammed with vials populated with fruit flies and the usual good strong cuppa. Fruit flies are no house flies: each adult fly is only a few millimetres long, their beautiful bodies are pale with black zebra-like stripes and their eyes a bright apple-red colour. I grabbed a vial, fired a puff of carbon dioxide gas through its fluffy plug and then firmly rapped the upended vial to shake its sleepy occupants onto an illuminated pad. I took a deep breath before peering at them through the eyepieces.

At the time, I was more than mid-way through my doctoral studies, and the results of my experiments were far from extraordinary. I was researching the most common genetic killer of human infants, a neuromuscular degenerative disease known as spinal muscular atrophy or SMA in short. I was exploiting the tiny fruit fly to gain new insight into this catastrophic disease.

I decided to up my efforts by generating a series of mutants or faults in Gemin3, the gene that I was investigating. I was targeting these mutants to different organs such as brain, muscle, or gut. The results of this screen were due today. With a few flicks, I deftly flipped and sorted the minuscule fly bodies into neat piles taking note of differences that are invisible to the untrained eye. The mutants did not produce any dramatic effect. Damn! Another experiment down the drain! Frustrated by the result, I mistakenly knocked over a vial, dislodging its plug. Usually, released flies would happily escape by flying. Strangely, my flies were jumping as if attempting flight but just couldn’t make it into the air — an unexpected but interesting trait or phenotype. I checked the tag on the vial. In these flies the mutant was targeted to that part of the body that powers movement, the so-called ‘motor unit’. Following that afternoon, which will remain forever etched in my memory, the results just flowed in and a few months down the line I would find myself donning my subfusc (Oxford-speak for academic dress) to defend my doctorate.

Fly Superstar

The rise to biological stardom for the fruit fly, scientifically known as Drosophila melanogaster, began in 1907 when my great-great-grandfather (by academic lineage) Thomas Hunt Morgan adopted this organism to understand heredity or genetics. Morgan was the first to harness the major advantages of working with this organism: they have an insatiable sexual appetite and a speedy development (only 10 days) from embryo to adult. This means that large-scale experiments are doable in record time. Morgan’s infamous ‘Fly Room’ at Columbia University in New York set the stage for a new ‘religion’ practiced and preached across the globe.

Morgan spent years searching unsuccessfully for flies with clear, heritable  differences so that he could investigate how they are inherited. A breakthrough happened in April 1910 when he discovered his first mutant, a white-eyed male fly amongst many red-eyed flies. Morgan took great care of this special fly: he kept it in a bottle and after a day’s lab work he used to take it home! At the same time his wife Lilian, who also became a famous geneticist, gave birth to a child. And such was the excitement surrounding Morgan’s discovery that on his first visit to the hospital, Morgan’s wife said: ‘How’s the fly?’ To which, Morgan replied: ‘How’s the baby?’.

When the white-eyed fly was bred or crossed with a virgin red-eyed female, their offspring were all red-eyed. When sisters and brothers were crossed, half of the male progeny gained back their white-eye colour. This hereditary pattern is typical for a sex-linked (recessive) variation, since the gene for eye colour in Drosophila, named by Morgan as the white gene, is on the X chromosome which determines sex. Similar to us, male flies are XY whereas females are XX. This key experiment and numerous others that followed expanded on the knowledge gained through the ingenious cross-breeding experiments of pea plants by the Austrian monk Gregor Mendel half a century earlier. Importantly, this fly-based work found that characteristics like eye colour are inherited from parents through chromosomes — large structures which package DNA in our cells. Furthermore, Morgan and his gifted students uncovered that the thousands of genes in our genome are arranged along chromosomes in a precise order, like beads in a necklace. Each gene can be identified by its specific location on a chromosome.

“Flies could be used as models of human disease”

In 1933, Morgan won the Nobel Prize for these great discoveries. The first of six awards was to recognise seminal insights into our biology through this tiny fly. Hence, in 1946 one of Morgan’s protégés, Hermann Muller, was recognised for his fly research demonstrating that X-rays can damage chromosomes. Then in 1995, Ed Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus shared the Nobel Prize for their herculean efforts in discovering the genes that controlled early development in Drosophila. In the embryo, waves of master genes are triggered that lead to eyes, brains, and the body’s patterning. Similar genes were later found in humans doing the same function. In 2011 Jules Hoffman received the Nobel Prize for finding how the body’s inbuilt immunity works through the use of the fly model organism. I suspect that there is still room for more trophies in the fly triumph cabinet.

At the dawn of this century, the genomics revolution led to the complete DNA sequencing of an organism including fly and human. These monumental projects revealed that an astonishing number (more than two-thirds) of human genes involved in disease have counterparts in the fly. This development meant that flies could be used as models of human disease. It sparked off a renaissance of Drosophila research. The fly was good at modelling neuro-degenerative conditions because their nervous system has stunning similarities to ours. Neuro-degenerative diseases including Alzheimer’s, Parkinson’s, Huntington’s, and Motor Neuron Disease occur when neurons in the brain and spinal cord begin to die slowly. Patients may lose their ability to function independently or think clearly. Symptoms progressively worsen and ultimately, many die. Most neuro-degenerative diseases strike later in life, so we should expect their frequency to soar as our population ages — Alzheimer’s disease may triple in the US alone by 2050.

 

Malta: the right time to fly?

Together with my students in my lab at the University of Malta I am working with flies to learn more about neuro-degenerative disease. We continue to focus on SMA, a genetic disorder arising from the deterioration of motor neurons which are nerves that communicate with and control voluntary muscles. As the motor neurons die, the muscles weaken with drastic effect on the walking, crawling, breathing, swallowing, and head and neck control of unfortunate children afflicted by this condition. The child’s intellectual capacity is unaffected but vulnerability to pneumonia and respiratory failure means that many patients die a few years after diagnosis.

The underlying cause of SMA is usually a gene flaw that results in low levels of a protein called SMN for survival of motor neurons. Inside cells, SMN is bound to other proteins called Gemins. The SMN-Gemins alliance is involved in building the spliceosome, which is the chief editor of messenger RNA molecules. Messenger RNA carry the DNA code that instruct cells how to fabricate proteins. If SMN is absent spliceosomes do not form, correctly-edited messenger RNA are not produced and protein synthesis is heavily disrupted — the cell should shut down. Spliceosomes are required in each of the 120 trillion cells forming our body. Yet, in the disease SMA only motor neurons die. The reason has baffled researchers for decades and remains unsolved.

Is it possible that SMN has another function in motor neurons? And does it act alone? Our flies were crucial in providing some answers to these questions. Our work showed how the SMN-Gemins family is tightly-knit. In this regard, we recently demonstrated that both SMN and Gemins can be detected in prominent spherical specks in different cellular compartments. Within the cytoplasm, these organelles are known as U bodies because they probably are the factories of spliceosome components, which themselves are rich in the chemical Uridine. In the nucleus, the structures containing the SMN-Gemins family hug the mysterious Cajal bodies — discovered over a century ago by Spanish Nobel laureate Santiago Ramón y Cajal.

“We are feeding these flies the Mediterranean diet derivatives to see whether Alzheimer’s can be stopped in flies, which will bring us one step closer to treating it in humans”

And what about the flightless flies? Think about it. Considering that SMA is a neuromuscular disease, it makes perfect sense that on loss of SMN, muscles become so weak that flies are unable to flap their tiny wings fast enough to fly. Our latest work reveals that flightlessness is seen in flies without enough Gemin proteins. This means that SMN does not function alone but hand in hand with the Gemins. Our next step was to find out the pathway connecting the SMN-Gemins family to the motor defects. We linked the Gemin mutant which did not work properly to a tag called green fluorescent protein or GFP. GFP glows under the right light in cells. We managed to create genetically-modified flies with this modified gene — a first for Malta and a powerful tool to solve the mysteries of this disease.

Fluorescent proteins let researchers figure out a protein’s location. And by knowing the location of proteins we gain of lot of information about what they do. Consider this analogy with a VIP. If we tagged the Prime Minister of Malta we would find that he is most probably found in Valletta most time of the year. If we were aliens from another planet, this knowledge would allow us to refine our understanding of the Prime Minister’s function. Therefore, we can eliminate a function in the entertainment industry (weak signal  from Paceville) but we cannot exclude a function in government (strong signal from Valletta). Likewise, we found that our GFP-Gemin mutant is mostly found in the cell’s nucleus. The nucleus houses life’s instruction manual: DNA. Our work now needs to zero in on the other proteins the SMN-Gemins family works with in the nucleus. Doing so will open new therapies to halt neuro-degeneration in children. Back to our analogy, we need to zoom in on Valletta until Auberge de Castille, the Prime Minister’s office, is clearly in focus.

Fly infographicSeveral neuro-degenerative diseases occur because of sticky protein clumps that wreak havoc inside, and outside, neurons. This is typical in Alzheimer’s disease, Parkinson’s disease and Motor Neuron Disease. With Dr Neville Vassallo’s research group, and local industry (Institute of Cellular Pharmacology), we are testing chemical derivatives of the Mediterranean diet and flora on fruit flies to see whether they can curb the protein clumps’ toxicity. They definitely do in a test tube. Flies mutated to be remarkably similar to human Alzheimer’s lose their ability to climb up the sides of their vial habitats and die prematurely because of neuro-degeneration. We are feeding these flies the Mediterranean diet derivatives to see whether Alzheimer’s can be stopped in flies, which will bring us one step closer to treating it in humans.

Through flies we have understood human biology. Apart from choosing Mr and Mrs Right, a good geneticist must learn to focus and listen to what flies are really saying. This is easier said than done but achievable. Flies have spurred me to pursue unexpected but interesting paths. In the years to come I, together with my students, will continue to flip, sort, screen and tag, looking for fly mutants who will continue to teach us about ourselves. And yes, we will be all ears!

 

The author is indebted to colleagues at the UoM and worldwide for their constant support and inspiration. The research of Dr Ruben Cauchi (Department of Physiology & Biochemistry, UoM) is funded by the Faculty of Medicine and Surgery, the University of Malta Research Fund and the Malta Council for Science & Technology (MCST) through the National R&I Programme 2012 (Project R&I-2012-066). For more about Dr Cauchi’s research click here.

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