A clear example of this change in behaviour is the energy production in cancer cells. In regular conditions and in the presence of oxygen, cells get energy (as ATP, an energy molecule) from glucose through different processes. The first one is called glycolysis.  This process doesn’t happen in any specific cellular compartment, but in its cytoplasm. The result of the glycolysis is a compound called pyruvate, which in the presence of oxygen, will be transformed by the Krebs Cycle to produce a high amount of ATP. The Krebs Cycle takes place inside the mitochondrias, the energy factories of the cell. However, when there is not enough oxygen, the pyruvate is transformed into lactate, through the anaerobic oxidation, in the cytoplasm with the production of a very low amount of ATP. All these processes are very well regulated and the cell can sense when there is something wrong in the mitochondria. If this happens the cell will activate an auto-destruction mechanism called apoptosis to avoid bigger problems.

During the 30’s Otto Warburg suggested a theory to explain some of the escape mechanisms of the cancer cells. He proposed a model in which the cancer cell would “switch off” its mitochondria and get the energy in the cytoplasm, even in the presence of oxygen, through an aerobic glycolysis. This theory, called the Warburg Effect, has been accepted for many years but how it happens exactly is not known yet. However, Professor Michael Lisanti’s group (where Stephanos Pavlides, who has helped with his knowledge to this article, works) has done several studies that are in contradiction with this theory. Cancer cells produce free radicals and, due to this, they live surrounded by oxidative stress. Researchers in Lisanti’s group were studying normal cells, called fibroblasts, that surround breast cancer ones. When they put together these normal fibroblasts and the cancer cells from breast cancer they saw that the oxidative stress produced by the cancer cells was affecting the normal cells as well. The free radicals, produced by the cancer cells, produced a process called autophagy, by which the cell “eats” its own components, in the fibroblasts. When this happens, pyruvate and lactate (the energetic molecules) are produced by the fibroblasts and taken by the cancer cells. In this way the fibroblasts are feeding the cancer cells promoting their growth and “switching their mitochondria back on”. If the mitochondria of the cancer cells are again on and there is no problem in them, the cells will escape the mitochondrial dependent auto-destruction (apoptosis). These researchers have called “The Reverse Warburg Effect” to the fact that the aerobic glycolysis doesn’t happen in the cancer cells but in the fibroblasts. In addition, the autophagy in fibroblasts produces more free radicals that will amplify the effect of the ones produced by the cancer cells promoting a higher amount of DNA damage in the cells. This damage is one of the reasons for genomic instability, one of the processes that can transform a normal cell into a cancerous one. In conclusion, cancer cells effect on fibroblasts behaviour promotes cancer cells feeding by the fibroblasts (producing the energetic compounds through autophagy), the fibroblasts help on the cancer cells evolution (producing DNA damage and genomic instability) and the protection against the apoptotic cell death (promoting the switch back on of the mitochondria in the cancer cells).

These conclusions came from previous studies in several labs where researchers discovered that low levels of a protein, called caveolin1 or Cav1, were related to aggressive and poor prognostic breast cancers. At the beginning they didn’t know exactly why this happened. However they saw that in tumors with very little Cav1 there was a high amount of proteins involved in glycolysis, meaning that these cells had a high autophagic activity. This happened in the cells surrounding the tumors (fibroblasts) and not in the proper cancer cells. Actually, the amount of Cav1 in the fibroblasts predicts cancer recurrence, metastasis and tamoxifen (common drug used to treat breast cancer) resistance of breast and pancreatic cancers, among others.

As you can see, this is a complicated but promising subject. Actually this effect can explain several facts related to the treatment of different cancers. One kind of treatment that has been tried, without success, is the therapy focused on inhibiting the formation of new blood vessels, or antiangiogenic therapy. Antiangiogenic drugs produce an oxygen decrease, or hypoxia, around the cancer promoting oxidative stress and autophagy. These conditions are ideal for cancer cells to grow and divide because they are fed by the nutrients produced by the surrounding fibroblast through autophagy.   

On the other hand, there have been some studies using drugs that block autophagy, preventing the fibroblasts digestion and subsequent release of nutrients for the cancer cells to use. Malaria drug chloroquine uses this mechanism and it would be very interesting to study its effect on cancer. In addition, drugs that supress mitochondria’s ability to use lactate and other glycolytic products could help block the energy supply of the cancer cells. Actually, one of these drugs used in diabetes treatment, metformin, has an effect on cancer cells. Diabetic patients who are taking metformin have less risk of having cancer. However, this hasn’t been scientifically proven.

In short, studying the processes of energy production and consumption, or metabolism, in cancer cells and their surrounding cells is a very promising research field, as well as the study of drugs already used for other diseases and their effect on cancer. This opens a new line of future cancer treatments that hopefully will have positive results and help decrease the mortality produced by this group of diseases called “cancer”.

References:

1: Pierotti MA, Berrino F, Gariboldi M, Melani C, Mogavero A, Negri T, Pasanisi P, Pilotti S. Targeting metabolism for cancer treatment and prevention: metformin, an old drug with multi-faceted effects. Oncogene. 2012 Jun 4. doi: 10.1038/onc.2012.181. [Epub ahead of print] PubMed PMID: 22665053.

2: Sotgia F, Whitaker-Menezes D, Martinez-Outschoorn UE, Flomenberg N, Birbe RC, Witkiewicz AK, Howell A, Philp NJ, Pestell RG, Lisanti MP. Mitochondrial metabolism in cancer metastasis: visualizing tumor cell mitochondria and the “reverse Warburg effect” in positive lymph node tissue. Cell Cycle. 2012 Apr 1;11(7):1445-54. Epub 2012 Apr 1. PubMed PMID: 22395432; PubMed Central PMCID: PMC3350881.

3: Witkiewicz AK, Whitaker-Menezes D, Dasgupta A, Philp NJ, Lin Z, Gandara R, Sneddon S, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Using the “reverse Warburg effect” to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers. Cell Cycle. 2012 Mar 15;11(6):1108-17. Epub 2012 Mar 15. PubMed PMID: 22313602; PubMed Central PMCID: PMC3335917.

4: Maycotte P, Aryal S, Cummings CT, Thorburn J, Morgan MJ, Thorburn A. Chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy. Autophagy. 2012 Feb 1;8(2):200-12. Epub 2012 Feb 1. PubMed PMID: 22252008; PubMed Central PMCID: PMC3336076.

5: Ahn JH, Ahn SK, Lee M. The role of autophagy in cytotoxicity induced by new oncogenic B-Raf inhibitor UI-152 in v-Ha-ras transformed fibroblasts. Biochem Biophys Res Commun. 2012 Jan 13;417(2):857-63. Epub 2011 Dec 21. PubMed PMID: 22206679.

6: Witkiewicz AK, Kline J, Queenan M, Brody JR, Tsirigos A, Bilal E, Pavlides S, Ertel A, Sotgia F, Lisanti MP. Molecular profiling of a lethal tumor microenvironment, as defined by stromal caveolin-1 status in breast cancers. Cell Cycle. 2011 Jun 1;10(11):1794-809. Epub 2011 Jun 1. PubMed PMID: 21521946; PubMed Central PMCID: PMC3142463.

7: Bonuccelli G, Whitaker-Menezes D, Castello-Cros R, Pavlides S, Pestell RG, Fatatis A, Witkiewicz AK, Vander Heiden MG, Migneco G, Chiavarina B, Frank PG, Capozza F, Flomenberg N, Martinez-Outschoorn UE, Sotgia F, Lisanti MP. The reverse Warburg effect: glycolysis inhibitors prevent the tumor promoting effects of caveolin-1 deficient cancer associated fibroblasts. Cell Cycle. 2010 May 15;9(10):1960-71. Epub 2010 May 15. PubMed PMID: 20495363.

When Mounira Hmani-Aifa of Tunisia won the UNESCO-L’Oréal International Fellowship in 2002, she used it to do postdoctoral research in human genetics at the Faculty of Health Science in Linköping, Sweden. Back in Tunisia, she continues to study the genetic origins of hereditary deafness in the laboratory directed by Professor Hammadi Ayadi. In addition, as a part of a bilateral project between Tunisian and Swedish teams, she started a new genetic study on posterior microphthalmia, a rare hereditary disorder affecting the eyes.

RESEARCH THAT HELPS FAMILIES

Having recruited some Tunisian families in collaboration with ophthalmologists and otolaryngologists, she succeeded in discovering some of the genes responsible, making possible genetic counselling for affected families. Mounira plans to use her 2012 Special fellowship to further investigate and interesting lead turned up by research concerning a posible link between one of the genes she discovered and glaucoma. “Once we understand how the genes intervenes,’ she says, ‘maybe someday it will lead to treatment.”

THE CHALLENGE: DOING IT ALL

The Special Fellowship rewards excellence and perceverance in the career of a former International Fellow, and Mounira has shown a singular determination in pursuing her work while maintaining the balance of her family life. Married ‘to and understanding scientist’, the molecular biology professor Mohamed Sami Aifa, with four children, she holds a full-time teaching job at the Faculty of Sciences, yet still manages to continue her research and publish frequently in prestigious scientific journals, and also to participate in sports, socialize, read (on religion, culture and philosophy) and even join an association for women’s rights, La Femme Libre. ‘I want to do everything!’ she says. She is hoping that, under the new government in Tunisia, researchers will no longer be required to teach full time, allowing her more time for lab work. She does not see any special difficulty in being a female scientist in her country, where she notes that more women than men have PhDs in science. ‘My problems – family life, pregnancy, children- are the same as those of my French and Swedish friends,” she says.

INSPIRED ‘TO BE THE BEST’

Mounira credits her parents for her successful career and particularly her late father : ‘The challenge he gave us was to be optimistic and hopeful. He told us we were capable of doing whatever we wanted to do.’ Confronted with a choice between going to work as a teacher to help the family or continuing her studies, her father told her : ‘Don’t think about money. We don’t want you to work now; we want you to be the best!’ Although as a teenager she was interested in going into cancerology, Mounira ultimately chose genetics instead. ‘In 1997, it was an exciting new fields’, she  points out, ‘and I was interested in how we could help families with hereditary diseases.’

2 months after participating in the L’Oréal-UNESCO Awards ceremony in Paris, Ingrid Scheffer referred to this experience as a key moment in her career. She had to talk to the media and learn how to deal with the limelight.  “Science is sexy, and it is our job to tell everyone that.”

Ingrid Scheffer is convinced that scientists have a responsibility to communicate, not only with the scientific community (scientists are sometimes seen as living in ivory towers) but with a wider community. Communication in science is based on both publications and conferences. “We publish or we perish”, she said in front of an audience of students.

Most of all, communication is about sharing ideas. Team work is essential. That’s why attending international conferences is an important part of a scientific career.

Ingrid Scheffer is a pediatrician. In her field, communication also means sharing with patients. Enthusiasm about the results and their implications helps the patients to fight the disease.

LESS IS MORE

Prof. Scheffer’s advice to students: when it comes to communication, keep it simple.

“It’s very important to have a framework to your talk, said Scheffer. When you present your research, you have to keep in mind that people in the audience are not familiar with your topic. A big mistake:  We don’t stand back and give the big picture. We can explain the context of what we are talking about. You know your work so well, but nobody has a clue of what you’re talking about.

“We all like complexity and you can make a talk very complex but it is not necessarily a good talk. A good talk makes it simple but importantly:  everything must be as simple as possible but not simpler.”

WORKING WITH THE MEDIA

“We are scared of the limelight.” Scientists have to talk to everyone. “Media try to translate. But we have to help them. You have to deliver your message synthetically.”

Journalists are keen to get a story and scientists have to find a way to give them that story. Most of the time, the media are more interested in writing about the results, than in explaining the research process. Talking with the media is also an opportunity for scientists to raise awareness with the general public and to influence science policy.

 Ingrid Scheffer mentioned her colleague Bonnie Bassler (L’Oréal-UNESCO Awards Laureate For North America) as her “idol” in science communication. Her famous TED Talk remains the best example for any researcher who wants to get people excited about science. 

 Ingrid Scheffer is a paediatric neurologist and professor at the University of Melbourne. Her research aims to help to transform the diagnosis and treatment of epilepsy, a brain disorder characterized by seizures and other sympltoms that can be extremely disruptive to the lives of the 50 million people affected by it.

 Definition of success

 On the one hand, there is this widely extended idea that to be a successful scientist you need to be well known between your peers, and/or win the Nobel prize, publish hundreds of papers in high impact  journals, and of course put aside your personal life. Am I right? There are two problems with this definition. Number one, as Sheryl Sandberg mentioned in her magnificent TED talk,  you might be tempted to “leave before you leave”. Which means you won’t consider moving forward in your career because you expect that you won’t make it, or that you’ll have to sacrifice a lot (when you actually can’t know what will happen in the future, can you?). And number two, the pressure is so high that you don’t even consider other options. And so, you just move with the crowd, following the path that you are supposed to take.

 That definition of scientific success doesn’t necessarily need to be yours. If it is, good for you. But if it’s not, do you really want to keep going or “leave before you leave”, and find yourself in the middle of nowhere in a few years?

 It’s important that you decide what you want, and what your definition of success is. And then, yes, to keep moving forward. Whether you want to win the Nobel and work 12 hours a day, or you prefer to work less and spend more time doing different things, it’s your decision. There is no right or wrong decision in this matter. What is important is that, as the years go by, you feel satisfied with your decisions. You don’t have to make all your decisions right now, but can do so when the moment comes. There is no point in deciding during graduate school that you don’t want to pursue a  scientific career because you plan to have children ten years from now. Cross that bridge when you get there. Meanwhile, do what you really want to do now. Don’t “leave before you leave”. And of course, don’t do what you are “supposed to” if it’s not what you really want to do.

  The impostor syndrome

 The second obstacle you might experience during  your career is the impostor syndrome, which is defined as the inability to accept your own success by Dr Pauline Clance and Dr Suzanne Imes (Psychother. Theor. Res. 15, 241–247; 1978). It’s the feeling that tells you that you are not as smart as everyone thinks you are. That all your labmates are smarter than you are, and you ended up there almost miraculously, not because you are an intelligent, smart and perfectly capable person. These feelings are very frequent in brilliant people, and can jeopardize your career. Your lack of confidence might lead you to reject opportunities because you feel you wouldn’t measure up.

 If this is your case, you need to know that about 70% of people feel this way at various points in their careers. Fortunately, in most cases, it passes as you get more experienced. But if it doesn’t, it’s important that you know that without exception, people suffering from the impostor syndrome are smart, brilliant and talented. The only problem is that they don’t believe they are. You can find more information about it on Dr Valerie Young´s website.

 Feeling like a failure

 Lastly, I’d like to talk about a feeling very frequent in scientists who are considering leaving academia. Feeling like a failure. Apparently it’s extremely difficult to make the decision to leave academia without feeling like a failure, even if your new job is related to Science in some way. That makes the decision very painful, and in some cases it leads to not make the  move even though you’d really love to. Why? Because:

 1. That’s not what you are “supposed” to do. Why leaving academia after investing so many years?

2. You don’t think you can do anything besides being a scientist.

3. What if you regret it?

4. Changing careers equals failing in your head. “Everyone” knows that if you leave that means you are not good at it, that you are a failure. Right? NO!

I’ve been through all those stages, and if you are in this situation you probably will too. It’s normal, it’s OK and it will pass. But I want you to keep three things in mind:

1. A career is not a life sentence. You can change your mind, and experience different things.

2. Changing careers has nothing to do with being good enough (in any case it would show that you are braver than the rest, and that you are good at more than one thing!)

3. You are not your job. It’s easy to identify yourself with your job, and then feel at a loss if you change that job, because you’ll feel you have lost your identity. Please know that you are much more than your job title.

 If you are considering changing careers but don’t want to feel like a failure, you need to know that you probably will, for a brief period of time. But feeling like a failure can actually be something good. Just yesterday I read a sentence by the marketing expert Marie Forleo that summarizes it perfectly:

  “Feeling like a failure is a natural part of becoming a success. It’s actually a good thing and means you’re taking action and putting yourself out there. Which is WAY more than most critics and naysayers have the balls to do” ( you can read her whole post here).

 What do you think? Being aware of these 3 roadblocks is the first step to moving past them. Have you experienced any of them yet?

About the author : Aida Baida Gil, PhD is a certified coach and former geneticist. She helps scientists and professional women around the world to decide the next step in their careers and to make career changes. You can contact her at www.experimentyourlife.com

Professor Colin Blakemore, Oxford University, Chairman of the Selection Committee said: ‘Together, the work of these two Europeans scientists illustrates the value and power of interdisciplinary approaches in neuroscience, and the way in which cutting-edge fundamental research is needed to understand complex clinical problems and to accelerate benefit for patients’…….’We are delighted that The Brain Prize for the best of European neuroscience goes, in its second year, to two women scientists. We are sure that the award will be applauded by female researchers around the world, and by all those who are concerned that young women are given every encouragement to consider careers in science’

The prize lectures and award ceremony will take place 9th May in Copenhagen, Denmark.

THE WORLD IS HER LAB

Even as a 7-year-old girl, Susana López could not contain her curiosity about the natural world. As a  child she was fascinated by flies, ants and even lizards.This scientific bent stood her in good stead when it was time to choose a path in life. Becoming a scientist was an obvious choice.Today, the little girl who enjoyed experimenting is still doing research, but in a far more disciplined and meaningful way. The ultimate goal of her work is to help children all over the world by cracking the code of the highly infectious and often deadly rotavirus, which affects millions of children. While a vaccine now exists, the war has not yet been won in developing countries, where it kills about 600,000 children every year.

‘This is a very democratic virus,’ she says, ‘in the sense that children get sick from it the same in Finland as in Africa.’ The problem in developing countries, she explains, is that it is difficult to get sick children, who quickly become severely dehydrated, to a doctor or hospital on time for rehydration, without which they may die.

TRACKING A VIRUS

Susana López’s research goal is to understand how the rotavirus infects human cells. ‘We are trying to learn the tricks the virus uses to conquer  the cell,’ she says, explaining that viruses are like parasites, which cannot replicate outside of the host cell, which they usually kill or weaken. The immune system cannot attack the invader, as it would with bacteria, without harming the cell, and anything a drug does to prevent the replication of the virus may also hurt the host cells.

This knowledge could lead to the eventual development of an antiviral drug that would control the infection, a notoriously difficult task. So far, antivirals are available only to prevent the replication of very specific viruses, such as HIV, herpes, and influenza A and B.

Professor López can’t predict how long it might take to develop such a drug, but in any case, that is not her job as a basic researcher, a profession she loves. ‘I like working in science because you are always learning new things. Even after 30 years of working with this virus, we’re still learning new things every day. There are new technological and methodological approaches we can use, so it’s always fun.’

Susana Lopez (L'Oréal-UNESCO Laureate 2012) with her team

RIGOR AND CREATIVITY

Part of the fun for her is the creativity required for her research. ‘You need to be rigorous because you need to be constant, to pursue one idea, but you also need to be creative,’ she says. ‘That’s the only way you can make science. If you don’t want to repeat yourself, you needto imagine new things all the time.’ She especially enjoys bouncing ideas off others to come up with new ideas, a process she calls ‘borrowing brains’. When she was young, there was little encouragement for students to follow careers in the sciences in her all-girl high school, but she did have some talented biology and chemistry teachers who inspired her to continue as well as her parents, who ran a pharmacy. Originally she planned to become a physician, but soon realized she would rather work on discovering the origins of illnesses in the lab.

Professor López has had no problems combining a career and family life, since she and her husband, biochemist Carlos Arias Ortiz, shared equally the responsibility of raising their son and daughter, who are now in their twenties. When she is not working, she loves to relax with Latin American novels or thrillers, cook Indian and Mexican food, especially historical recipes, and practice photography.

As a woman living in Mexico, Susana López sees herself as a double minority in the world of science. Her dearest wish is to serve as an example for others, to show ‘that you can be whoever you want to be wherever you are, as long as you work hard. I am very proud, because we were able to show that we can do excellent basic science in Mexico.’

As spring turned to summer in South Africa in late 2011, Professor Farrant was enthusiastically watching the reaction of a plant she had recently discovered that is the only one known to transition into a drought-tolerant state when the dry season arrives. ‘It’s starting to switch on the right genes,’ she said, adding, ‘To look at the signals involved is awesome.’

Jill Farrant (2012 L'Oréal-UNESCO laureate)

She speaks about the resurrection plants she studies – which have the fascinating ability to revive from a dried-out, seemingly dead state to full, green life when given water – almost with affection. ‘They have a special place in my life,’ she admitted. In fact, these plants carry a certain symbolism for Jill Farrant. Like the plants that are the subject of her research, she has undergone something of a resurrection. Three years ago, she suffered a head injury that brought her within an hour of death. Coming back to life after that traumatic experience has been a mighty struggle – not least because she has since lost her senses of taste and smell – but one that has enabled her to find a new balance between her work and private life. Her goal now is ‘to be able to live on a day-to-day basis with happiness and serenity and passion for whatever I do, be it my work or people or my hobbies.’

 AN EARLY PASSION FOR NATURE

Professor Farrant’s desire to be a scientist and her interest in resurrection plants both stem from her childhood on the family farm. ‘I spent a lot of time on the farm on my own,’ she says, ‘and my passion for nature started there.’ When she was nine years old and an avid birdwatcher, she was sitting one day in a favourite place called the Flat Rocks and noticed that what had seemed to be a dead plant on a rock had come alive again after it rained. She still has the diary in which she noted the experience: ‘The ded [sic] plant on the rocks was alive but Dad wouldn’t believe me.’ A memorable trip to the Solomon Islands when she was 18 convinced her that she should become a marine biologist. Later, she was inspired by her professors and role models Patricia Berjak and Norman Pammenter, a husband and wife team at the University of KwaZulu Natal, ‘my guiding lights, who have dedicated their whole life to science’ and with whom she still sometimes collaborates. ‘Science was always a passion,’ adds Jill Farrant, ‘and it just evolved.’

Later, the memory of the dead plant’s revival when she was a child inspired her to focus her research on resurrection plants when she returned to South Africa from the United States, where she had been studying for a year. Nelson Mandela had just been released from prison, and she had been offered a job at the University of Cape Town. She wanted to be part of the new South Africa. ‘I knew I could make a difference,’ she said. ‘It’s really important to educate people so they can make informed decisions. That’s why I came back.’ 

 FIVE YEARS TO DROUGHT-RESISTANT MAIZE?

While the holy grail of her research is to make possible the development of drought-resistant crops, some of these plants may also have ‘very promising medicinal uses’ that she is not yet prepared to talk about. How long might it be before these dreams become reality? ‘How long is a piece of string?’ she asks. ‘It’s not just about finding a whole set of genes that seemingly are required for drought tolerance. You’ve got to look at the whole plant physiology in order to understand what protective processes are involved and how these, in turn, are regulated at the molecular level.’ That said, she thinks that pre-commercial production of drought-tolerant maize varieties might be possible in five years. ‘But you never know,’ she cautioned.

WACKY IDEAS AND LATERAL THINKING

Professor Farrant, who describes herself as a spiritual person who delights in understanding God’s creation and who often communicates with Him in nature, is so passionate about every aspect of her work, from basic research to teaching, that she has trouble choosing one that interests her more than others. ‘I am fascinated with the applications,’ she said. ‘I would like to understand what plants are doing, how they do it, what their signalling molecules are, how they talk to each other. I would, of course, love to find a solution to world problems like food security. That would be a big thing for me. But you get there slowly, step by step.’ One of her gifts, she believes, is to have ‘wacky ideas’ that lead her into new areas. This kind of lateral thinking is something that she appreciates about working and brainstorming with other women. She also channels her creative streak into writing poetry and songs, and recently bought herself a piano and plans to teach herself how to play.

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THE EXHILARATION OF DISCOVERY

 Science has always been an all-consuming passion for Frances Ashcroft. ‘To make a discovery, to know that you are the person who’s seen something for the very first time, is the most exciting thing in the world’, she says. ‘It is really extraordinarily exhilarating. When that’s happened to you once or twice, you are hooked for life. And that exhilaration sustains you throughout the long years of work in the lab.’

Frances Ashcroft insists that credit be shared with the many lab members and colleagues she has worked with over the years. ‘Science is a team effort’, she says, ‘and no-one walks alone’. Nevertheless, she alone was responsible for the discovery that made it all possible 25 years ago, when she found the ion channel that is the missing link between glucose and insulin secretion. Glucose stimulates insulin release by closing this channel (a tiny pore in the cell membrane). Another breakthrough came in 1995, when Professor Ashcroft and others elucidated the DNA sequence that codes for the channel. This enabled them to screen the DNA of people with diabetes for mutations (variants) in the channel genes. Then in 2003, her friend and colleague, Professor Andrew Hattersley, found a mutation in the channel gene in a patient with a rare inherited form of diabetes that develops within the first few months of life. Ashcroft’s team showed the mutant channel was no longer closed by glucose, thus explaining the patient’s diabetes. Importantly, they also found that the channel could still be closed by sulphonylurea drugs. At that time, people born with diabetes were treated with insulin injections, as their symptoms suggested they had an unusually earlyonset form of type 1 diabetes (a disease in which the beta-cells are destroyed by the body itself and life-long insulin is essential). The work of the Ashcroft and Hattersley teams suggested that instead such patients could be treated with sulphonylurea drugs, which by shutting their open channels would stimulate insulin secretion from their own beta-cells. Over 90 percent of people with neonatal diabetes have now switched to sulphonylureas. This has resulted in improved blood glucose control and a better quality of life for hundreds of patients.

THE DOCTOR AS DETECTIVE

Ingrid Scheffer sees herself as a sort of detective. She collects clues from patients, their families, imaging and brainwave investigations, as well as specialists in a range of scientific disciplines, and then fingers the culprits: the various causes of epilepsy, the most common brain disorder affecting children. In all, around 50 million people worldwide have epilepsy, and they experience seizures of many types that vary in severity and length, often seriously impairing a person’s ability to lead a normal life. One of Professor Scheffer’s strengths is that she studies epilepsy from two vantage points, as a paediatrician who regularly sees and treats patients, and as a scientific researcher. These two distinct but highly complementary roles have contributed to the extraordinary success she has had in uncovering the genetic origins of many types of epilepsy.

Ingrid Scheffer (L'Oréal-UNESCO Awards 2012 - Laureate for Asia/Pacific)

For the Laureate from Australia, seeing patients in the clinic and doing research in the lab go hand in hand, feeding into and informing each other. ‘You have to look at patients and see what scientific questions they might be asking or answering,’ she says, ‘and then you take that back to a research setting and think about how you can try to answer that question.’ Success in understanding the underlying science means being able to help the patient directly. ‘You can see that you are really making a difference to their lives.’ That has already happened as a result of her work on Dravet syndrome,for example, a severe form of epilepsy that starts at the age of about six months. Ingrid Scheffer and her colleagues were the first to show that sodium channel genes caused febrile seizures. This led to a Belgian discovery that sodium channel gene mutations caused Dravet syndrome, later confirmed by Ingrid Scheffer and her collaborative group. This genetic information has already impacted on a selection of the best treatments and genetic counselling for families. ‘Whilst we can’t fix those mutations – I hope one day we will be able to – we know that if you have that diagnosis, certain drugs work, while others might make you worse. We’ve already seen that my research has had a lot of applications, and the field is only in its infancy.’

NEW THINKING FOR AN OLD DISEASE

 
During her career Professor Scheffer has often had to buck accepted wisdom about epilepsy. When she was training at the Great Ormond Street Hospital for Sick Children in London, where she did her first research projects, and was about to embark on her epilepsy training in Melbourne, she told her mentor that she was thinking about doing her PhD in genetics of epilepsy. ‘You’ll never get anywhere with that,’ he said. ‘To his credit,’ says Ingrid Scheffer, ‘10 years later he sent me an e-mail saying he was wrong. We’ve made a big difference to people’s understanding of genetics and epilepsy. People now recognize that it often has a genetic component.’

In Melbourne, she works closely and happily with Professor Samuel Berkovic, with whom she runs a research group. ‘He is my mentor and my friend and the biggest influence in my life academically,’ she says. Although she has won major international awards, recognition has been slow to come in her own country. ‘Overseas there’s no question that I am recognized in my own right as a leader, but in

Australia it’s been a real issue.’ Other people who have influenced Professor Scheffer’s choice of a career in medicine and research were her mother, a nurse educator, and her disabled brother, who died when he was 20 and she was 18. ‘His illness impacted greatly on my life, so I think that helps me understand more what the families I look after are going through.’

Pr Ingrid Scheffer with her students

ENJOYING THE JOURNEY

 
Today, Ingrid Scheffer wears many hats: paediatric neurologist, head of a hospital children’s department, researcher, professor and international lecturer. She jokes that all these activities leave her only from ‘midnight to 3am’ to enjoy her hobbies: reading, baking, travelling and spending time with her husband and sons, especially walking the dogs and going out to dinner with her two sons, the great pride of her life.

One has decided to follow in his mother’s footsteps as a physician-scientist and is already studying medicine.

Professor Scheffer admits to having great fun with her work, feels very privileged to work with such wonderful families and colleagues, and has a few words of advice for budding scientists: think outside the box, take your time and enjoy the journey.

This bacterial communication is called quorum sensing (QS).

Although the first discoveries in the field of bacterial communication where made more than 40 years ago in the marine bacterium Vibrio fisheri (1), they simply did not have the quorum to be heard. Until Bonnie Bassler came along… Thanks to Bonnie and her colleagues, today, microbiology courses throughout the world include QS as part of its syllabus.

And the story of QS is not just a tale for scientists, it affects all of our lives.

Like many other discoveries in science, this one too began by a stroke of luck.

During her PhD, Bonnie Bassler attended her first ever conference in Baltimore, where she quite accidentally heard the one-in-a-ten-year talk of a reclusive geneticist, Professor Mike Silverman, who reported his studies on bioluminescence in the marine bacterium V. fisheri. Being a chemist, she admits to not understanding much of what Silverman was talking about, yet she knew, this is what she wanted to do. ‘I have to work on this or I’m going to quit science!”’ she remember saying to herself.

Bonnie Bassler (Laureate of the 2012 L'Oréal-UNESCO Awards) with her students

A “genius” MacArthur fellow

The ubiquiitousity of QS in the bacterial kingdom and its importance, surpassed even Bassler’s imagination admitting; “we always knew we were working on something bigger than bioluminescence, but we didn’t think it would be what it turned out to be. It’s just been so much better”

Bonnie Bassler and V. harveyi, glowing in the dark: "it would be fantastic if out of this crazy glow-in-the-dark bacterium that came out of the ocean, something really really good, like a new antibiotic, came out of this guy,"

 Further discoveries in other bacteria revealed that all bacteria are using one form, or another of QS to coordinate group behavior (5-8). This was a major discovery, because it meant that this in not an anomaly restricted to harmless marine bacteria that communicate to produce light, but it also used by the most deadly human pathogen to achieve successful host infection.

 So… if we can break the code, eavesdrop the conversation, manipulate the information, we could interfere with bacterial communication to coordinate their attack and thereby prevent disease. A whole new class of bacterial antibiotics. Unlike most common antibiotics, aimed at killing bacteria, a practice which promotes the development of antibiotic resistant strains, this new class of antibiotics would aim to disrupt bacterial communication. Simply preventing bacteria from talking to, or hearing each other and activating their vicious group behavior.

Bassler have already discovered QS antagonist which were shown to disrupt bacterial pathogenesis, preventing it from killing its host, in this case the model organism, Caenorhabditis elegans, a microscopic warm (11), opening a window to this potentially new antibiotic.

 Bassler, a pioneer in the field of bacterial communication, a Howard Hughes scholar and a member of the National Academy of Sciences, wants to put things in perspective when she says, that basic science is great, but she would really want to do something practical, “I want to actually, in my life time, help people”, putting the emphasis on generating knowledge for the purpose of solving our problems.

 Bassler is richly deserving of the 2012 L’ORÉAL-UNESCO Award in Life Sciences for “For understanding chemical communication between bacteria and opening new doors for treating infections”. She is still very much engaged in elucidating the secretes of bacterial communication and finding ways to manipulate this knowledge for the benefit of all of us.