fungi in science

The University of Aberdeen Fungal Group was awarded £5.1M to tackle fungal infections

2012-02-22T19:28:00.000Z

The University of Aberdeen Fungal Group has been a awarded a Wellcome Trust Strategic Award to lead a UK collaboration to bring fungal science closer to treating infection.

The new Medical Mycology and Fungal Immunology Consortium aims to train a new generation of scientists and clinicians but also to promote greater public awareness of fungal infections.

Professor Al Brown (right), a chair in Microbiology at the University of Aberdeen and Co-Director of this Consortium, also coordinates the FINSysB Network.

Read more about the award on BBC or the University website.

Lay summary: Candida albicans in different host niches

2011-10-02T21:02:00.001+01:00

Iuliana Ene works in the Aberdeen Fungal Group at the University of Aberdeen. She and her supervisor, Prof. Alistair Brown, are interested in how available nutrients in host niches modulate the pathogenicity of C. albicans.

Dynamic environmental responses of Candida albicans that contribute to pathogenicity

Candida albicans isthe most common fungal pathogen in humans, causing a variety of health problems ranging from mucosal to systemic infections.Generally harmless, it is present in 40-80% of the normal population,but in immunocompromised individuals it can proliferate and access differentinternal organs and tissues causing potentially fatal infections.C. albicans occupies a number of different niches in the human host. This is where thepathogen is exposed to a variety of nutrients, many of themdifferent from more classical ones (e.g. glucose) which are the basis for moststudies conducted so far. Theshift from harmless commensal to opportunistic pathogen requires C. albicans’ ability to grow in poornutrient niches and survive the diversity of stresses it encounters in thehost.

Many of these stresses, such as therapeuticdrugs or osmotic stress act on the cell wall of the pathogen. This is the maininterface between C. albicans and itshost, a multi-layered interface which proves to be extremely flexible and dynamicwhen exposed to different nutrients. We are studying how the variety ofnutrients found in the host modulate adaptation and stress responses and how thecell wall must quickly adjust under these conditions. In doing so it relies onmechanisms of constant remodelling and maintenance of cell wall integrity. Moreimportantly we have found that certain nutrients and in particular poornutrient niches in the host provide a fitness advantage to the pathogen. Having adapted to these niches, C. albicans also increases itsresistance to a number of antifungals, which are currently the only availableweapon against fungal infections.

In this study,we show how the nutrients taken up strongly influence the cell wall architectureand hence resistance of C. albicans to certain stresses. These findings arelikely to have a major impact on the behaviour of this pathogen insidethe human host and may be of major clinical importance.

Adaptări dinamice la condiţiile de mediu care contribuiela patogenicitatea Candideialbicans

Candida albicans este agentul fungic patogen cel mai frecventla om, provocând o varietate de probleme de sănătate de la nivelul mucoasei lainfecţii sistemice. În general inofensiv, acest patogen este prezent în40-80% din populaţia normală, dar în cazul persoanelor imunocompromise poateprolifera şi avea acces la diferite organe interne şi ţesuturi, provocândinfecţii potenţial letale.

C. albicans ocupă diferite nişe în gazda umană, acest patogen fiind expus la o varietate desurse de carbon, multe dintre acestea diferind de zaharurile clasice (deexemplu, glucoză), care stau la baza majorităţii studiilor efectuate până înprezent. Trecerea de la comensalism la patogenicitate necesită abilitatea C. albicans de a prolifera în nişe săraceîn nutrienţi şi de a supravieţui diversităţii de factori de stress întâlniţi îngazdă. Mulţi dintre aceşti factori de stress, cum ar fi agenţiiterapeutici sau stresul osmotic, acţionează pe peretele celular al agentuluipatogen. Acesta constituie principala interfaţă dintre C. albicans şi gazdă, o interfaţă multi-strat, care se dovedeşte afi extrem de flexibilă şi dinamică atunci când C. albicans este expus la diferiţi nutrienţi. Acest proiect studiază modul în care varietateade substanţe nutritive întâlnite în gazda umană modulează răspunsurile deadaptare la stres şi modul în care peretele celular se adaptează continuu acestorcondiţii. În acest sens, se bazează pe mecanisme de remodelare constantă şi demenţinere a integrităţii peretelui celular. Mai important, am constatat căanumiţi nutrienţi oferă un avantaj de supravieţuire agentului patogen. Deasemenea, aceştia cresc rezistenţa la un număr de antifungice, care sunt în prezentdisponibile ca singura arma împotriva infecţiilor fungice.

În acest studiu, vom arăta cum substanţele asimilate influenţeazăputernic arhitectura peretelui celular şi, prin urmare, rezistenţa C. albicans la anumiţi factori de stres.Aceste constatări pot avea un impact major asupra comportamentului acestui agentpatogen în interiorul gazdei umane şi deci pot fi de importanţă clinică majoră.

Lay summary: Candida albicans and it's sweet tooth

2011-09-30T18:11:00.001+01:00

The FINSysB researchers are preparing for the final workshop and conference in Italy in the next two weeks. In today's post, Iryna Bohovych describes where Candida albicans gets it sugar and how it is affected by the availabilty of different sugars. She is working at the University of Aberdeen in Prof. Al Brown's lab and is interested in what role of sugars in an infection.

A sweet way to becomestronger: an example from human fungal pathogen Candida albicans

There are more than 300,000 known speciesof fungi, but only a few of them can cause human infections. One of them,Candida albicans, is a relatively harmless organism, which can occupy the skin,oral cavity gastrointestinal tract and genitalia of healthy people. However,this fungus can take and advantage of immune system defects and cause a widerange of affections from mild superficial thrush to fatal systemic infections.There are lots of factors which make C. albicans so effective pathogen; amongthem are the ability to consume different nutrients (e.g. sugars) and to resistto different stresses.

When C. albicans cells enter thebloodstream, they are attacked by host cells, phagocytes, which cause oxidativestress to fungal cells. Also, in the human they are exposed to glucose in thebloodstream. Thus, we hypothesized that nutrients sensing might influence stressresponses. Indeed, in laboratory environment C. albicans cell, exposed toglucose, became more resistant different stresses. Also, it was less sensitiveto killing by neutrophils, cells isolated from human donors, when glucose wasadded. Using different types of modified glucose we have been able to provethat C. albicans cells just need to sense glucose, not necessarily to consumeit, in order to become more resistance to oxidative stress. C.albicans, likeother yeasts, has 3 distinct mechanisms for glucose sensing, which form acomplicated network. We are now investigating the role of major components ofthis network in the phenomenon of glucose-enhanced oxidative stress resistance.

Сладкий способстать сильнее: пример патогена человека Candida albicans

Среди 300 000 известных видов грибовтолько несколько способны вызывать заболевания человека. В их числеотносительно безвредный организм Candida albicans, населяющий кожу, ротовуюполость, желудочно-кишечный тракт и половые органы человека. В условияхдефектов иммунной системы этот грибок может вызывать целый ряд заболеваниячеловека, от легкой поверхностной молочницы и до летальных системных инфекций.C. albicans является настолько эффективным патогенном благодаря целому рядуфакторов, среди которых способность употреблять разнообразные питательныевещества (например, сахара) и противостоять стрессам.

Когда C. albicans попадает в кровь, еесразу же атакуют клетки хозяина, фагоциты, которые подвергают клетки грибкаоксидативному стрессу. В то же время в организме человека этот микроорганизмсталкивается с глюкозой. Таким образом, у нас возникла гипотеза о влияниисенсинга (опознания) питательных веществ на ответ на стресс. Действительно, влабораторных условиях, клетки C. albicans после короткой инкубации с глюкозойставали более резистентными к разным видам стресса. Также эти клетки были менеечувствительны к уничтожению нейтрофилами, изолированными со здоровых доноров.Использую разные типы модифицированной глюкозы, нам удалось доказать, что дляклеток C. albicans необходимо всего лишь определить наличие глюкозы в среде длятого, чтобы стать более резистентными к оксидативному стрессу. C. albicans, каки другие дрожжи, имеет 3 разных пути сенсинга глюкозы, объединенные в сложнуюсеть. Мы пытаемся изучить роль основных компонентов этой сети в феноменеповышенной резистентности к оксидативному стрессу в ответ на наличие глюкозы.

Солодкий спосібстати сильнішим: приклад патогена людини Candida albicans

З-понад 300 000 відомих видів грибівлише кілька можуть викликати захворювання людини. Одним з них є Candidaalbicans, відносно безпечний організм, що може населяти шкіру, ротовупорожнину, шлунково-кишковий тракт та статеві органи здорової людини. Однак заумов порушень роботи імунної системи цей грибок може викликати ряд захворювань,від легкої поверхневої молочниці і до фатальних системних інфекцій. C. albicansє настільки ефективним патогеном за рахунок цілої низки факторів, серед яких єздатність споживати різноманітні поживні речовини (наприклад, цукри) тапротистояти стресам.

Коли C. albicans потрапляє в кров, то їїодраз ж атакують клітини господаря, фагоцити, що спричинюють оксидативний стресклітин грибка. В той же час в організмі людини цей мікроорганізм стикається зглюкозою. Таким чином, у нас виникла гіпотеза про вплив сенсингу (впізнання)поживних речовин на відповідь на стрес. Дійсно, в лабораторних умовах, клітиниC. albicans після короткої інкубації з глюкозою ставали більш резистентними дорізних видів стресу. Також ці ж клітини були менш чутливими до знищеннянейтрофілами, ізольованими зі здорових донорів. З використанням різних типівмодифікованої глюкози нам вдалося довести, що для клітин C. albicans необхіднолише виявити наявність глюкози в середовищі для того, щоб стати більш опірноюдо оксидативного стресу. C. albicans, як і інші дріжджі, має 3 окремі шляхисенсингу глюкози, що об’єднані в складну сітку. Ми намагаємося з’ясувати рольосновних компонентів цієї сітки у феномені підвищеної резистентності дооксидативного стресу у відповідь на наявність глюкози.

Lay summary: Clinical relevant stresses and the cell wall

2011-09-28T19:29:00.002+01:00

Another day, another lay summary. Today, Alice Sorgo, working at the Universiteit van Amsterdam in the Netherlands. In the group of Dr. Frans Klis she is interested in how Candida albicans copes with medical relevant stresses that it encounters in the patient. This research will lead in the future to better targeting of new antifungals and a more effective therapy regime.

Dynamics of cell wall and secreted proteins of the pathogenicfungus Candida albicans in response to clinically relevant stress conditions

The fungus Candida albicans is living in the majority of thehuman population usually without having any effect on their health. Sometimesit causes relatively mild superficial infections. Nevertheless, when the host’simmune system is severely weakened, C. albicans can gain access to thebloodstream and spread throughout the whole body. If not detected and properlytreated in time a bloodstream infection is able to rapidly kill the patient.Conventional methods for diagnosis take two days, making faster diagnosticsnecessary. New resistances emerge against the already existing antifungal drugsresistances, hence new antifungal treatments are needed.

The wall proteins and secreted proteins of C. albicans arevery dynamic under changing environmental conditions. These proteins play animportant role for C. albicans fitness and virulence. They serve fundamentalroles, like tissue adhesion and invasion, biofilm formation, nutrientacquisition and defense against the host’s immune system. In the human host C.albicans has to cope with a variety of challenges. It grows in sites whereoxygen levels are high, like on the skin, as well in niches where very lowoxygen levels are found, such as in the gut. C. albicans is able to acquireiron, which is rarely found in a freely available form in the human body but isessential for its survival. It also adapted to survive in the presence ofantifungal drugs and at high temperatures, like during fever.

We are investigating how the cell wall and secreted proteinsof C. albicans contribute to the fungus’ survival and virulence under thesemedically relevant stress conditions. We are applying mass spectrometry tomeasure qualitative as well as quantitative changes of these proteins thatmight help C. albicans adapting to these conditions. Our research will improvethe understanding of how C. albicans copes with various infection-associatedstress conditions as well as how cell wall and secreted protein levels arecontrolled. Importantly it might lead to the identification of new potentialtargets for vaccine development and diagnostic markers.

Dynamik der Zellwandproteine und sekretierten Proteine des pathogenenPilzes Candida albicans als Antwort auf klinisch relevante Stressbedingungen

Candida albicansist ein Pilz der in den meisten Menschen lebt ohne Einfluss auf derenGesundheit zu haben. Manchmal kann er jedoch eine oberflächliche Infektion derSchleimhäute verursachen. Bei Patienten deren Immunsystem ernsthaft geschwächtist kann C. albicans bis in die Blutbahn vordringen und sich im ganzen Körperausbreiten. Wenn eine solche Infektion nicht rasch diagnostiziert und richtigbehandelt wird endet das in den meisten Fällen tödlich für den Patienten.Herkömmliche Diagnosen nehmen zwei Tage in Anspruch, was die Entwicklung schnellererMethoden notwendig macht. Gegen die kommerziell verfügbaren Antimykotikaentwickeln sich immer mehr resistente Pilzstämme, somit ist es notwendigständig nach neuen Antimykotika and Behandlungsarten zu suchen.

DieZusammensetzung der Zellwandproteine und sekretierten Proteine ändert sich jenach der Umgebung in der C. albicans sich befindet. Außerdem sind dieseProteine unverzichtbar für Fitness und Virulenz des Pilzes. Sie dienengrundlegenden Funktionen, wie etwa der Anhaftung und Einwanderung in dasGewebe, der Bildung von Biofilmen, der Aufnahme von Nährstoffen und derVerteidigung gegen das Immunsystem des Wirtes. Das Leben in einem Wirt bringtviele Herausforderungen mit sich. C. albicans wächst an sauerstoffreichenOrten, wie etwa der Haut, aber auch an Orten an denen Sauerstoffarmutvorherrscht, wie etwa im Darm. C. albicans ist außerdem in der Lage das für dasÜberleben notwendige Eisen zu erlangen, obwohl dieses im Wirt kaum freizugänglich ist. Der Pilz hat sich so weit angepasst, dass es ihm sogar möglichist in der Gegenwart von Antimykotika und hohen Temperaturen, wie zum Beispielwährend eines Fiebers, zu überleben.

Wir erforschenwie Zellwandproteine und sekretierte Proteine dem Überleben und der Virulenzdieses Pathogens während medizinisch relevanter Stressbedingungen dienen.Mittels Massenspektrometrie messen wir qualitative und quantitativeVeränderungen in der Zusammensetzung dieser Proteine, welche dem Pilz bei derAnpassung an diese Bedingungen hilft. Unsere Forschung wird das generelleVerständnis darüber verbessern wie C. albicans verschiedene Stressbedingungenbewältigt und wie Zellwandproteine und sekretierte Proteine kontrolliertwerden. Schlussendlich könnten neue Angriffspunkte für die Impfstoffentwicklungund Diagnose von Candida Infektionen ermittelt werden.

Lay summary: Zinc uptake in Candida albicans

2011-09-27T17:44:00.002+01:00

In our continuing coverage of our FINSysB film stars, today Dr. Francesco Citiulo. He is working at the Hans-Knoell-Institute in Jena, Germany in Prof. Hube's group. He is trying to understand how Candida albicans aquires zinc in the host where it is kept scarce.

Characterization of molecular mechanism used by fungal pathogens to uptake Zinc from host cells during the infection

Fungal pathogens are a significant cause of morbidity and mortality and resistance to current antifungals limits the effectiveness of treatment. Targeting the access of the fungus to host nutrients represents an exciting new area of therapeutic development. A variety of metals are important for pathogenic fungi to grow and to establish an infection. For example, iron is known to be sequestered by the host to prevent the growth of pathogens in a process known as nutritional immunity. However, Candida albicans is able to acquire host iron, and the molecular mechanisms underlying this have begun to be unraveled.

Zinc is an important metal for both the host and any invading pathogen. Recently, it has been shown that the natural antimicrobial peptide, calprotectin, is highly expressed in the human body in response to infection and chelates zinc. This points to the possibility of an important role of host zinc for the pathogen to establish an infection.

Using C. albicans as a model, our aim is to characterize the molecular mechanisms that pathogenic fungi use to acquire zinc from the host. By an in silico analysis on the C. albicans secretome we identified multiple Zn binding domains in 35 kD secreted protein , this protein is interestingly highly conserved throughout the fungal kingdom. Using a deletion strain for this protein and other molecular tools, including a gene reporter we have already shown that zinc is important for C. albicans growth and that the 35 kD secreted protein plays a pivotal role in host cell damage via Zn-acquisition.

Therefore, we have begun to uncover the molecular mechanism by which C. albicans acquires Zn from host cells. The future goal will be to fully characterize the molecular bases of the mechanism that C. albicans uses to sequester Zn, useful for growth, from the host. The knowledge obtained from these studies will lay the foundation for the future creation of peptides that could inhibit Zn uptake from the host by pathogenic fungi restricting their ability to establish an infection.

Caratterizzazione dei meccanismi molecolari usati dai funghi patogeni per catturare Zinco dall’ospite durante il processo d’infezione.

I funghi patogeni sono una significativa causa di malattia e mortalità, la resistenza che essi sviluppano agli antifungini limita l’efficacia dei trattamenti odiernamente usati per eradicarne l’infezione. Un’interessante area di ricerca sullo sviluppo di nuove terapie per le infezioni fungine è basata sulla creazione di molecole che impediscono al fungo l’acquisizione di nutrienti dall’ospite. L´accesso ai metalli dell’ospite da parte del fungo è, infatti, uno step molto importante per il processo d’infezione; per esempio il ferro è sequestrato dall’ospite per prevenire la crescita del patogeno, in un processo conosciuto come immunità nutrizionale. Candida albicans ha sviluppato meccanismi per circonvenire questo processo e acquisire ferro dall’ospite; le basi molecolari di questo meccanismo sono in corso di studio.

Lo zinco è un metallo importante sia per l’ospite sia per il patogeno. Recentemente è stato dimostrato che la calprotettina, un peptide a funzione antibiotica prodotto dall’uomo, è altamente espressa durante un infezione microbica o fungina ed essa sequestra lo zinco. Questo mette in evidenza la possibilità che l’accesso allo zinco dell’ospite da parte del patogeno giochi un ruolo chiave nell’infezione.

Usando C. albicans come organismo modello, il nostro scopo è quello di caratterizzare i meccanismi molecolari che i funghi patogeni usano per acquisire lo zinco dall’ospite. Mediante un’analisi in silico del secretoma di C. albicans abbiamo identificato una proteina di 35kD, con omologhi in altri funghi patogeni, che contiene multipli siti di legame per lo zinco. Usando un ceppo di C. albicans deleto per questa proteina e altri tool molecolari incluso un gene reporter, abbiamo dimostrato che lo zinco è essenziale per la crescita di C. albicans e che la proteina 35kD ha un ruolo chiave nel processo d’infezione, rendendo lo zinco dell’ospite accessibile al fungo.

Il nostro futuro goal è quello di caratterizzare le basi molecolari di questo meccanismo che permette a C. albicans di sequestrare lo zinco dell’ospite. Le conoscenze derivanti da questo studio saranno le basi per la sperimentazione di nuovi composti che consentiranno di bloccare l’accesso di varie specie di funghi patogeni allo zinco dell’ospite limitando così la loro capacità di creare un infezione.

The flash game Pandemic 2 let's YOU be the infectious disease!

2011-09-25T21:09:00.001+01:00

To effectively fight any enemy, you have to understand it first. This is one of the most basic principles when you are trying to prevent infectious diseases. But every disease and its causative agent are different. Modes of infection, transmission, outside host survivability, symptoms and especially the underlying molecular biology is hard to pin down and explain with only one model. But there are still a couple of basic principles that are very nicely illustrated in the game Pandemic 2 below.

In this game you take on the role of an infectious disease. You can choose between being a virus, bacteria or a parasite (no fungi though, sorry). Then you are directly thrown on a world map. Congratulations, you just infected your first human in a random region of the world. Each region is characterized by a set of variables and measures taken by the government to control your disease. Many regions have ship yards and airports that are instrumental in spreading the infection. Also, national water supplies and hospitals are important factors.

While randomly occuring natural disasters helps you, governments will hinder you by taking increasingly drastic measures.

The effectiveness of your disease depends basically on three variables. Lethality does exactly what it says on the box, a measure of how fast your disease kills an average human. Infectivity tells you how well the disease is transmitted and spreads through a population. Finally, Visibility determines how fast authorities react to your disease by closing airports, harbors, public transport and so on. For example, in the games term, the Ebola virus would have a high lethality, a medium infectivity but it would be very visible while HIV/AIDS would have a low visibility with medium infectivity and lethality. You can increase these variables by buying new traits with evolution points that are awarded for meeting certain milestones (number of infected, spread to a new region etc.).

Buying new symptoms, resistances and ways of transmission will affect the three key variables in different ways.

The game is relatively straight forward and has a good tutorial so just give it a try and see how you do. But it makes you realize how easily diseases can develop and spread. You also notice how hard the job of national and international health organizations like the WHO is to actually contain and combat a disease. So next time someone asks you what you did in your coffee break, just say you wiped out mankind. But remember, Madagaskar is always the hardest place to get. Enjoy!

Lay summary: Antifungal drug development

2011-07-26T14:27:00.004+01:00

As promised, this week it is Kate's turn to summarize her work. Kate is working with F2G Ltd. in Manchester to develop antifungal drugs based on essential genes.

Investigating new drug leads for fungal infections

Aspergillus fumigatus and Candida albicans are fungal species that can cause serious, often fatal, disease in the vulnerable, especially cancer and AIDS patients. Current medicines to treat these infections have many drawbacks including serious side effects and limited effectiveness. This project aims to find new leads in the fight against these kinds of infection. A molecular approach has been used to find proteins that are essential for the survival of both A. fumigatus and C. albicans. The theory is that if these essential proteins are disabled the fungal cells will die. Therefore it is hoped that finding chemicals that disrupt these proteins will provide chemical leads for antifungal drug discovery.

To date 3 proteins have been identified that are essential for the survival of both types of fungi. The 3 essential proteins have been made in large quantities using bacterial cells and screens are being developed to test for activity of the protein. Measuring activity of the protein in the presence of a library of small molecule compounds will enable identification of chemical inhibitors. Chemicals that disrupt both A. fumigatus and C. albicans proteins will be analysed in further detail to identify the best starting points for drug design. It is important that a new drug has the ability to enter cells in order to disrupt the protein inside the cell and cause cell death. This will be tested by mixing the chemicals of interest with whole cells to see if they can enter and then kill the cells. It is also important that the chemicals are not toxic to human cells. One way of testing this is to grow mammalian cells in a test tube in the presence of the chemicals and see if the cells stay alive. Other considerations are how easily the drug compounds can be manufactured, costs and intellectual property surrounding the work.

This study should result in new broad-spectrum antifungal drug leads to fight two of the most medically important fungi. Newer, effective antifungal medicines will result in huge benefits to human health.

FINSysB video

2011-07-15T09:17:00.006+01:00

This week we have something very special for you. During our last workshops in Berlin and Jena a video for our public dissemination video was shot. With Kate, Neelam and Francesco as our stars, the video gives an overview of what we do and why we do it. Have a look and let us know what you think. Next week, Kate will explain more about her project in her lay summary. Stay tuned and enjoy.

Lay summary: Candida albicans and cells of the immune system

2011-06-15T13:23:00.018+01:00

Today's lay summary is about how the immune system is dealing with Candida albicans cells if they are encountered. Pedro Miramón is working at the HKI in Jena under the supervision of Professor Bernhard Hube. He is trying to understand the interplay between Candida albicans and specific immune cells, called neutrophils. His summary is available in english, spanish and german. Incidently, it is also Pedro's birthday to day so happy Birthday and keep up the good work!

Understanding the response of the human fungal pathogen Candida albicans to the attack by immune cells

Candida albicans is a fungus commonly associated with humans without causing any harm. The reason this fungus is usually harmless is because immune cells constantly patrol the sites in the body where the fungus lives; for example, the oral cavity or the gut. However, under certain circumstances, C. albicans is able to surpass the vigilance of the immune system, causing a variety of diseases ranging from superficial non-lethal manifestations to life-threatening deep-seated infections.

The purpose of this project is to understand how C. albicans is recognised and eliminated from the host. To this end, we are studying how the cells of the immune system fight against the pathogen. The key players involved in eliminating not only fungal, but pathogens in general, are phagocytes – specialised cells from the immune system which engulf and kill microorganisms. We know that C. albicans responds differently to the several kinds of cells found in blood. The cells that evoke the most dramatic response from the fungus are the so called neutrophils, cells of the immune system that play a major role in inflammation and the clearance of pathogens.

We aim to identify components of the fungal cell (proteins or enzymatic activities) that are involved in the response towards the attack by neutrophils, in order to better understand the response of the fungus and the strategies it uses to overcome and survive attack by neutrophils.

We have found that C. albicans responds in a different manner depending on whether it is inside or only touching the neutrophils. For instance, inside the neutrophils, we have observed that C. albicans produces proteins that neutralise potent oxidants that could kill the fungus. Some of these proteins are produced even before the fungus comes in contact with the neutrophil, preparing itself to encounter the oxidants and hence, survive. When the fungus is unable to produce these proteins, its survival is decreased in the presence of neutrophils. We have also observed that the fungus changes its metabolism to adapt to the nutrient-deficient environment inside the neutrophil.

Understanding the response of the fungus when confronted with phagocytes will allow us to identify the most important steps that lead to a proper response in order to contain the growth and dissemination of this opportunistic pathogen.

Entendiendo la respuesta del patógeno humano Candida albicans al ataque de células del sistema inmune.

Candida albicans es un hongo comúnmente asociado a los humanos sin causar daño alguno. La razón por la cual este hongo es generalmente inofensivo es porque las células del sistema inmune vigilan constantemente los sitios del cuerpo donde el hongo vive, por ejemplo, la cavidad oral o el intestino.

Sin embargo, bajo ciertas circunstancias, C. albicans es capaz de evadir la vigilancia del sistema inmune, provocando una variedad de enfermedades que van desde manifestaciones superficiales no letales hasta infectiones profundas que ponen en riesgo la vida.

El objetivo de este proyecto es entender cómo C. albicans es reconocida y eliminada del huesped. Para este fin estamos estudiando cómo las células del sistema inmune luchan contra el patógeno. Los principales actores involucrados en la eliminación de patógenos en general, no solo hongos, son los fagocitos – células especializadas del sistema inmune, encargadas de atrapar y matar microorganismos. Sabemos que C. albicans responde diferencialmente a los ditintos tipos de células que se encuentran en la sangre. El tipo de células que induce la respuesta más dramática por parte del hongo son los llamados neutrófilos, células del sistema inmune que juegan un papel muy importante durante procesos inflamatorios y durante la eliminación de patógenos.

Nuestro objetivo es identificar componentes del hongo (proteínas o actividades enzimáticas) involucrados en la respuesta hacia el ataque de los neutrófilos para comprender mejor esta respuesta, así como las estrategias empleadas para superar y sobrevivir al ataque de los neutrófilos.

Hemos encontrado que C. albicans responde de formas distintas dependiendo de si se encuentra dentro o sólo en contacto con los neutrófilos. Por ejemplo, dentro de los neutrófilos, hemos observado que C. albicans produce proteínas que neutralizan potentes oxidantes capaces de matar al hongo. Algunas de esta proteínas son producidas incluso antes de que el hongo entre en contacto con el neutrófilo, preparándose para encontrarse con oxidantes y, de esta manera, sobrevivir. Cuando el hongo es incapaz de producir esta proteínas, su sobrevivencia está disminuida en presencia de los neutrófilos. Hemos observado también que el hongo cambia su metabolismo para adaptarse a las condiciones deficientes en nutrientes dentro del neutrófilo.

Al comprender la respuesta del hongo cuando se enfrenta a los fagocitos, podremos identificar los eventos clave que llevan a una respuesta correcta para contener el crecimiento y la diseminación de este patógeno oportunista.

Wie der humanpathogene Pilz Candida albicans die Attacken des Immunsystems übersteht

Candida albicans ist ein Hefepilz, der häufig als harmloser Besiedler der menschlichen Haut und Schleimhäute vorkommt und unter normalen Umständen keinerlei gesundheitliche Schäden verursacht. In der Mundhöhle oder im Darm verhindern die Zellen des menschlichen Immunsystems effektiv, dass der Pilz Schaden anrichtet. Unter bestimmten Bedingungen kann C. albicans aber der Kontrolle des Immunsystems entgehen und dann verschiedenste Erkrankungen hervorrufen. Diese reichen von oberflächlichen und vergleichsweise harmlosen Verlaufsformen bis hin zu lebensbedrohlichen, systemischen Infektionen, die den ganzen Körper und verschiedene Organe betreffen.

In diesem Projekt soll daher versucht werden, die Erkennung und die Bekämpfung von C. albicans durch den Wirt besser zu verstehen. Wir untersuchen dazu, welche Mechanismen die Zellen des Immunsystems entwickelt haben, um C. albicans zu kontrollieren. Besonders wichtig sind dabei die sogenannten Phagozyten, Fresszellen des angeborenen Immunsystems, die Mikroorganismen in sich aufnehmen und dann zerstören können. Sie sind auch die ersten Immunzellen, mit denen C. albicans (und auch andere Krankheitserreger) im Wirt in Kontakt kommen sobald der Pilz in Gewebe eindringt. Dabei reagiert C. albicans in unterschiedlicher Weise auf die einzelnen Zelltypen der Immunabwehr. Besonders die neutrophilen Granulozyten, die an Entzündungsprozessen und an der Beseitigung von Pathogenen beteiligt sind, führen zu einer deutlichen Antwort des Pilzes.

Wir wollen deshalb Bestandteile der Pilzzelle (insbesondere Proteine und aktive Enzyme) identifizieren, die an der Interaktion von C. albicans mit neutrophilen Granulozyten beteiligt sind. Das soll uns ermöglichen, die Reaktionen des Pilzes besser zu verstehen – und damit seine Strategien, den Kontakt mit Immunzellen zu überleben.

Wir konnten schon zeigen, dass C. albicans – je nachdem, ob sich der Pilz im Inneren der Neutrophilen befindet oder nur an deren Oberfläche – unterschiedlich reagiert. Beispielsweise haben wir beobachten können, dass C. albicans innerhalb der Immunzellen ein Protein bildet, das Oxidantien unschädlich macht, die sonst den Pilz abtöten können. Einige dieser Proteine werden vom Pilz sogar schon gebildet, bevor er überhaupt mit Neutrophilen in Kontakt kommt. So kann er sich vor oxidativem Stress schützen und sein Überleben sichern. Ohne diese Proteine überleben deutlich weniger C. albicans-Zellen den Kontakt mit neutrophilen Granulozyten. Außerdem haben wir beobachten können, dass C. albicans seinen Stoffwechsel an die nährstoffarme Umgebung innerhalb der Neutrophilen anpassen kann.

In Zukunft wollen wir so die Reaktion von C. albicans auf Immunzellen besser verstehen und dadurch diejenigen Mechanismen identifizieren, die das Wachstum und die Ausbreitung des Pilzes im Körper ermöglichen.

Pedro Miramón

Lay summary: Wall proteins of Candida albicans

2011-04-13T16:30:00.015+01:00

Today will be the launch of a series of posts that will focus on the particular work of individual scientists of the FINSysB network. We are trying to describe our work as easy as possible for the lay men to understand and as a special treat the summaries will be translated in the researcher's mother tongue below. We hope you enjoy reading the summaries as much as we enjoy doing the research.

Wall proteins of Candida albicans as new targets for diagnostics and treatment of systemic fungal infections

Patients with a weakened immune system and especially in intensive care units are increasingly contracting fungal infections. These infections are often life-threatening. Candida albicans is the most common of these infectious fungi. Depending on how suppressed the immune response is, this can lead to unpleasant infections of the skin and mucosa, but also invasive, blood stream infections. Usually, almost half of these infections are fatal within a week, highlighting the need for faster diagnostics and better preventative measures, i.e. a vaccine.

The first contact with the host cell is established by proteins on the wall of the fungus. They have been shown to play a crucial role in both infections and resistance to the immune system. We are particularly interested in this layer of proteins that is directly attached to the cell wall of the fungus or is released into the environment. Environment specific changes are important for C. albicans to thrive in different niches in the host during an infection. We also are interested in how the predominant growth form change in C. albicans, from spheric yeast cells to elongated hyphal cells, affect the proteins on the wall.

The goals of my project are three fold. Firstly, we want to increase the basic understanding of these attached wall proteins and the secreted proteins and how their composition and abundance changes in infection related conditions. To this end, we want to quantify the wall proteins using mass spectrometry. Secondly, we want to develop methods that allow faster diagnostics based on these secreted proteins that are abundant in many growth conditions. Thirdly, we want to identify targets for the development of a vaccine against C. albicans. To identify parts of the proteins that are suitable for vaccine development, we will use prediction algorithms to assess their ability to elicit an immune response. Using these results we will assemble and test a vaccine protein that is comprised of the most immune-stimulating peptides of these proteins.

Zellwandproteine als Ziele für neue Diagnose- und Therapieansätze gegen systemische Pilzinfektionen durch Candida albicans

Patienten mit geschwächtem Immunsystem und speziell auf Intensivstationen erkranken immer häufiger an Pilzinfektionen. Diese Infektionen sind oft lebensbedrohlich. Candida albicans ist der am häufigsten vorkommende Erreger von Pilzerkrankungen. Abhängig vom Immunstatus der Patienten können unangenehme, aber relativ harmlose Infektionen der Haut und Schleimhäute, aber auch zu invasive, lebensbedrohliche Blutbahninfektionen auftreten. Üblicherweise verlaufen fast die Hälfte aller Blutstrominfektionen bei nicht rechtzeitiger Behandlung innerhalb einer Woche tödlich. Diese Tatsache unterstreicht die Notwendigkeit zur Entwicklung neuer und schnellerer Diagnoseverfahren und besseren Präventionsstrategien, zum Beispiel durch die Entwicklung eines Impfstoffes.

Der Erstkontakt zur Wirtszelle wird durch Proteine auf der Zellwand des Pilzes etabliert. Es wurde bereits gezeigt dass, diese Proteine eine essentielle Rolle beim Widerstand von C. albicans gegen das Immunsystem und bei Infektionen spielen. Unserer besonderes Interesse gilt hierbei jenen Proteinen, welche direkt an die Zellwand gebunden sind oder in die Umgebung abgegeben werden. Umgebungsbedingte Veränderungen dieser Proteine sind wichtig für C. albicans um in den verschiedensten Nischen des Wirts während einer Infektion zu florieren. Weiterhin sind wir daran interessiert, wie die wichtigste Veränderung in der Wuchsform, von runden Hefezellen zu verlängerten Hyphen, die Proteine der Zellwand beeinflusst.

Es gibt drei Hauptziele meines Projekts. Erstens, wollen wir die gebundenen Zellwandproteine und die sekretierten Proteine sowie Änderungen in ihrer Zusammensetzung und Menge unter Infektionsbedingungen grundlegend besser verstehen. Zu diesem Zweck setzen wir Massenspektrometrie ein um die Zellwandproteinmenge zu bestimmen. Zweitens, wollen wir basierend auf sekretierten Proteinen, die in vielen Wachstumsbedingungen gehäuft vorkommen, diagnostische Marker und Methoden entwickeln. Drittens, wollen wir vielversprechende Ziele zur Impfstoffentwicklung identifizieren. Mithilfe von Prognosealgorhythmen, bestimmen wir Teile dieser Proteine die in der Lage sind eine starke Immunreaktion auszulösen. Basierend auf diesen Ergebnissen stellen wir ein Impfstoffprotein zusammen, das aus den am immune-stimulierendsten Teilen dieser Proteine besteht, um es anschliessend zu testen.

Databases: The Facebook of the Molecules involved in Life

2011-03-04T00:42:00.005Z

The objective of biomedical scientists is to discover new medicines to cure diseases and to be able to detect them with new techniques which are more rapid, cheap and precise. In this field of research an enormous amount of information is generated with very powerful equipments (such as the ones used for the HUMAN GENOME PROJECT), producing huge files containing the sequence of nucleic acids (DNA, RNA) and protein sequences, protein 3D structures, and so on. So, where can we store all of this information? And how can we access them quickly? Where can we read scientific articles without going to the local library? The answer to all of these questions is the same: databases.

The databases are mainly maintained by big research associations such as EBI (the European Bioinformatics Institute) which is European or the NCBI (National Center for biotechnology information) which is American. As it was mentioned previously in our Scientific Collaborations article, the interaction between different organisms allows this to be possible.

In the NCBI database you can explore the gene region (literally walking among the chromosomes , as if you were using Google Maps), see the variations among people, check the protein database, You can also find PubMed, the bibliographic database; GenBank, the nucleotide sequence database; and the BLAST algorithm for sequence comparison, and so on. Similar results can be found in the Ensembl database.

If you are interested in proteins, you can check out the uniprot/swissprot database, where you can find biological information, the secondary structure of the protein (based on real-life experiments), the sequence of the protein and the bibliography. And even more interestingly, you can check the 3D structure of the proteins (based on real-life experiments as well) in the Protein Data Bank, you can find related information of the protein, bibliographic references, and the most exciting part, you can play with the Jmol viewer, moving the protein, and if you have the right pair of glasses, you can watch it in real 3D (yes, like in Avatar).

And exactly as on Facebook, you can check the “Friends” list of the molecule of interest, which could be the protein coded by this gene, related publications, gene ontology (gene and gene product information in several species), and so on, because all of this information is interconnected. The swissprot database is famous for having the links well up-to-dated. Moreover, you can find the “Photos” of the molecule of interest.

Before spending a lot of time and money in crazy experiments you can take a look on this databases to see if somebody else did the same experiment on the same molecule before or in a similar one which you can transfer information from. The best part is that if you don't know how to use these tools you can just click on the tutorial link and they have even videos where you can learn how to play with them! Scientists use these tools everyday in the lab before designing an experiment or when analyzing results, and even more, bioinformaticians (nerdy scientists than only use computers for their research) can even publish articles only by analyzing the information of this databases and using other programs to generate predictions, models or deep analysis of this information.

To summarize, databases are a user-friendly and open access way to obtain biologically relevant information which is used worldwide in research institutes, hospitals, industries and universities.

Diana Rosentul

Scientific collaborations

2011-02-25T10:10:00.011Z

Science doesn't happen in a vaccum. Despite the fact that scientist are usually depicted as recluses that spend the majority of their days (and nights) in the lab chasing new ideas and doing experiments, scientists are actually quite communicative. You could almost refer to them as social butterflies (in their field at least). The reason for that is quite simple. Specialization is the key not only in science but also in real life. Or, in other words, would you preferred to have your taxes done by an accountant or your butcher?

Most scientists are specialist in a defined field so that they can focus on solving a particular problem. The problem with too much specialization is that you lose track of the big picture and neglect to integrate your research with other results. Collaborations are the remedy to this problem. If scientists encounters a phenomenon that can not fully describe by their methods and experiments in which they are specialized, they turn to other experts in their field that have access to other methods, instruments or area of expertise. Of course, as a young researcher you don't have a large network available to you but usually you are introduced by your supervisor, make contact after talks or poster sessions at conferences or just have a drink with the people you want to talk to at the hotel bar. Scientists are a very open group of people because we all share the same idealism about research and progress. The pictures in this blog post show the scientific collaborations in the World and Europe from 2005 to 2009 and are courtesy of Oliver Beauchesne and flowing data.com. Also check out the zoomable worldmap here.

Most scientific papers that are written are not the product of a single group of researchers in one lab but by a number of groups that all contribute. These contacts are mainly made during scientific conferences or in research networks (like the european FINSysB network). By pooling their resources researchers are able to produce more and better research than they could if they were working alone. The exchange of ideas is at the very core of science right next to the scientific method and peer review. So the next time you see a single scientist saving the world in his small lab without ever talking to anyone in a movie or on television, you know how likely that is...

Paul Stamets on 6 ways mushrooms can save the world

2011-02-11T23:20:00.002Z

An interesting yet lively talk from TED - Paul Stamets believes that mushrooms can save our lives, restore our ecosystems and "terraform other worlds in our galaxy by sowing a mix of fungal spores and other seeds to create an ecological footprint on a new planet"

Let's talk about Candida albicans!

2011-01-31T14:44:00.010Z

After starting this blog with a couple of posts about scientific concepts and a few ways to play with biological information let me tell you a bit more about our research interest today. Candida albicans is the core focus of the european FINSysB research network. It is comprised of eleven internationally renowned labs from all over Europe as well as an industrial partner, F2G Ltd. ,for quick translation into the clinic. Usually, most research papers in our field start with a statement such as: "C. albicans is ordinarily found as a commensal yeast colonizing the human gastrointestinal tract."; "The opportunistic fungal pathogen Candida albicans is a leading cause of death in patients with fungal infections." or "Candida albicans is commonly found as a benign commensal in many warm-blooded animals. In humans it mainly resides on the skin and on mucosal surfaces without causing significant harm to the host."

But what does this actually tell you. Not a lot I guess. Basically, there is no reason to be afraid of Candida albicans if you are healthy and your immune system is in good shape. And even if not you shouldn't be alarmed because in most cases C. albicans is kept in check by the immune system. Some studies say that more than 80% of all humans carry Candida albicans on their mucosal surfaces and the gut. Most cases of fungal infections are either oral or vaginal thrush which are easily treatable by a capable physician and are unpleasant but not deadly.
The picture changes when C. albicans penetrates into the blood stream and/or the immune system is severely compromised as in ICU patients after major surgery or HIV patients. Here the mortality is going up to 40%, mainly because diagnostics are not fast enough and there are not enough effective antifungals available. The main problem here is that the fungal infection quickly disseminates to other organs, especially the kidneys, and destroys the tissue. In addition, in recent times Candida albicans is developing resistances to the few effective antifungals we have and evades treatment that way.
So the FINSysB consortium has several goals in which we hope to help treating clinicians as well as researchers in understanding both the inner workings of C. albicans as well as new treatment options. For that we defined four basic research areas: The "Fungal Armoury" is all about finding out how C. albicans is able to attack our cells and penetrate healthy tissue. Our body defends itself with "Defensive Shields"that kill of the fungus and prevent the infection from spreading. This battle is quite dynamic and a back and forth on the "Key Battlefields", mainly the surface of both C. albicans and our cells. Finally, we want to help to "Defeat the Enemy" by developing faster diagnostic methods, effective antifungals and ultimately a vaccine.
So have a look at our website, read about us in the European parliament magazine (page 78) or just comment if you have questions. But read our disclaimer first to avoid disappointment.

Playing with DNA can be fun!

2011-01-16T21:33:00.005Z

Happy New Year to everyone and although it is a little late (I know, I know) I thought we start it with a play section again. I am sure there was an uproar among all the geneticists that I choose a protein game for the first play post and not something with DNA. Also, the last game was a bit on the complicated side so today I want to introduce you to Phylo.

Phylo is a small flash game written by researchers from McGill University. They gave an important tool of genetic scientists, the so called Multiple Sequence Alignments, a bit more playful note. Multiple Sequence Alignments are used to see how similiar sequences from different species are and are therefore used to construct a tree of life starting from the origin of life. By seeing how similar sequences are, the relationship of species is revealed and how on species evolved out of another.

Since DNA is only composed of the four bases (Adenine, Cytosine, Guanine and Thymidine), Phylo replaces these building blocks by colored bricks. Your task is now to align two or more sequences to each other in that way that gaps in the sequence are minimized and a maximum of bricks of the same color are aligned. The program automatically scores you against a target value.

Normally this is done by computers which are good for a random aligning brute force approach but the human mind is a master in pattern recognition. Sometimes people can score higher than the computer just by intuition and a general feeling of what looks right. So to avoid spending an ungodly amount of money, they just harvest your free brainpower when you are taking a break and just wanna play something. So give it a try and see if you can help science in your lunch break.

How YOU can help science by solving puzzles

2010-11-25T10:06:00.011Z

The last few posts were mainly focused on concepts in science but today I just want to let everyone know of an easy way of helping biological science. The folding and conformation of proteins is essential for their function. From the DNA sequence, we can translate out of which amino acids the protein is made up and in which order they have to go. But the final structure is much more complicated to understand because a larger number of chemical bonds and interactions have to be take into account.

The program Foldit is a distributed computing application (like SETI@home where unused processing time of your computer is donated to sorting through radiotelescope data.) The difference between SETI@home and Foldit is that Foldit is looking to the smaller structure and therefore inward instead of outward. Foldit tries to simulate how a protein will fold when it is finished. The computer time you donate will be used to calculate the possible and impossible conformations for the protein.

Even better, you can even interact! Foldit is not a passive activity but fully interactive. because they are also trying to see if humans can improve computer predictions. Each protein is given to you first in an unfolded version (much like the translated product coming from the ribosomes). With a few tutorials and tools you are already able to fold proteins in their proper and most stable form. The picture below shows you the beginning of protein puzzle 48 (taken from Fold.it, links below).

The goal now is to fold it into the correct conformation as seen below.

Try it for yourself and see if you like it. Maybe next time instead of solving a crossword puzzle or doing a Sudoku, try folding some proteins and help science!

Koch's Postulates

2010-11-21T17:55:00.016Z

In my last post I was describing how scientists use the scientific method to keep their research objective. One of the best examples of applying the scientific method are Koch's Postulates. Robert Koch (1843-1910, left) was a german physician who was interested in how diseases are spread. He is considered the founder of modern microbiology and bacteriology together with his contemporary, Louis Pasteur (1822-1895, right).

In the course of his career, he developed countless microbial techniques that are still in use today. The Petri dish is named after his assistant. He identified the causative agents of Tuberculosis (Mycobacterium tuberculosis), Anthrax (Bacillus anthracis) and Cholera (Vibrio cholera). This earned him the Nobel prize for medicine in 1905.

One of his greatest contributions to microbiology was the formulation of the four Postulates that now carry his name. The postulates are step wise, each postulate based on the previous finding.
In order to establish that an organism causes a disease the following requirements have to be fullfilled:

Step 1: Association- The organism and the disease are observed together consistently.

Step 2: Isolation - The organism can be isolated from the diseased.

Step 3: Inoculation - The isolated organism causes the disease in a healthy individuum.

Step 4: Re-isolation - The organism can be re-isolated from the infected individuum.

Now look at each of these steps carefully and think about what they require you to do. Did you notice it? Between each of the steps the principles of the scientific method are applied. Here is a more graphic representation of the application of Koch's Postulates.

By putting clearly defined rules for what defines a disease causing organism (today referred to as a pathogenic organism or just pathogen), Koch made a major contribution to the then raging discussion about the cause and origin of diseases.

Before Kochs discovery of the Cholera bacterium, there was a heated discussion between the Contagionists and the Anticontagionists. The Anticontagionists (Max von Pettenkoffer was one of them, see also this post) argued that in their theory human-to-human transmission was only a very minor component. They were strong opponents of quarantine and disinfection because it inhibited trade and was less effective than local solutions like improved sanitation. You can read more about it here.

Koch's Postulates proved that transmissibility played an important role in epidemics and quarantines and disinfection was indeed a suitable method to counter both. In the end, everyone benefited from the discussion because it improved both local and global safety against infectious diseases. Getting scientists to agree to something is quite difficult but using the right arguments derived from proper use of the scientific method and you have a good chance of succeeding.

Next week I will write about the central dogma of molecular biology and why it is not so dogmatic anymore.

The scientific method

2010-11-19T16:35:00.007Z

In my previous post I was talking about the difficulty that scientists face to keep their research objective and unbiased. Luckily, smarter people than me have developed a basic set of concepts that help do that. All these concepts are mainly based on the Aristotelian laws of logic from the third century BC. Most of the ideas that define the scientific method nowadays are already described there. The scientific method is at the heart of science as a set of rules to make research as objective as possible. It is usually described in four basic steps.

Step 1: Observation and description of a phenomenon or group of phenomena.

Step 2: Formulation of a hypothesis to explain the phenomena.

Step 3: Use of the hypothesis to predict the existence of other phenomena, or to predict quantitatively the results of new observations.

Step 4: Performance of experimental tests of the predictions by several independent researchers and properly performed experiments.

Actually, people use these steps almost instinctively to predict cause and effect and adapt accordingly. For example, when you wake up in the morning, you look out of the window and see people on the street in cold weather clothing (Step 1, observation). Your hypothesis (Step 2) is that people are wearing warm clothes because it is cold outside (Step 3, prediction). To test your prediction you open a window or look at a thermometer (Step 4, Experiment). Usually the laymen abstain from enlisting independent researchers to do control experiments.

The scientific method has been refined over the centuries but the core of it is still untouched. The setup that is usually used as a checklist for adherence to the scientific method is the following:

Define the question
Gather information and resources (observe)
Form hypothesis
Perform experiment and collect data
Analyze data
Interpret data and draw conclusions serving as a starting point for new hypothesis
Publish results
Retest (frequently done by other scientists)

Notice point 6 which clearly shows that you normally refine your hypothesis based on the outcome of your first results. Most hypotheses defined by scientists continuously cycle between step 3 and 6 before they are ever published. The picture below describes the usual approach.

It is also important to note, that the scientific method doesn’t allow the absolute verification of a hypothesis. Einstein himself said: "No amount of experimentation can ever prove me right; a single experiment can prove me wrong." Especially physicists have a tendency to postulate an unknown factor, like the Higgs-Boson, to resolve issues with current theories. The current interest at the large colliders in Switzerland (Large Hadron Collider, CERN) and the US (Tevatron, Fermilab) is to experimentally proof whether or not the Higgs-Boson actually exists and has the properties that are required to make the theory behind it work.

If the Higgs-Boson could not be experimentally proven in the predicted range, most theoretical models of physics would have to be reexamined. I think that makes it slightly more understandable why there is so much money going into this kind of research because entirely rethinking physics sounds like a huge headache to me.

You can easily test what I said about the instinctive use of the scientific method. Just watch yourself and observe how your brain works and you draw conclusions about your environment. Or ask people how they arrived at the conclusion that it won’t rain today. But don’t let them get away with: “It never rains when I have an umbrella with me.” Maybe you can disprove that to them using the scientific method.

Have a nice weekend and keep on thinking!

2010-11-11T20:28:00.006Z

The above video was made with a 250,000 fps camera and captures a catapulting spore from a fungus. The organism, Pilobolus crystallinus, or more precisely - its spore, is said to be the fastest living thing in nature.

Here's a fragment from Richard Hammond's Invisible Worlds featured documentary on the same story:

Personal opinion and bias in science

2010-11-10T10:43:00.004Z

In my last post I was writing about how scientists are constantly looking for the big picture and more pieces of the puzzle. But how do we do that? What tools and techniques do we use? In the future we will describe specific techniques like imaging or mass spectrometry in this blog. But for now I would like to give a short introduction into the theoretical groundwork that every scientist uses. I hope that by explaining basic concepts in science it will help you to understand (and reality check) some or most of the news items that are published in non-scientific journals.

I often read something in the news about science that looks like a brilliant breakthrough and the journalist tries to suggest immediate applicability. In most cases it is just not as simple as that (especially not if it is written in the tabloids). Just because something was tested and worked in an animal model does not mean that it will work in exactly the same way in humans or soon. Sometimes it even has detrimental effects (London drug trial incident 2006). So I would like to explain a few basic concepts in science in my next posts. But first I want to highlight some problems that scientists face not only from without but also from within.

A major problem in science was (is?) the removal of personal opinion and bias. At some point people can get so invested in their idea that any other theory, observation or result must be wrong and can be explained away or faulted for some reason in some way. One of my favorite examples is the feud between Robert Koch and Max von Pettenkofer about the transmission of Cholera. Both brilliant scientists in their own right, they could never agree if Cholera, as it had been shown by Koch, can be transmitted from person to person and cause disease. This is one of Koch’s postulates, which I will address in a later post. Despite experimental evidence, Pettenkofer, aged 74, drank a pure culture of Vibrio cholerae, to show his opponent once and for all. He survived and just contracted light diarrhea and abdominal pain (he probably had contracted Cholera earlier in his life and this led to a lighter course of disease this time around). Pettenkofer saw that as irrefutable evidence that Koch was wrong.

Today we know differently but despite the fact that Pettenkofer was wrong in this instance he still was a brilliant scientist and one of the most important hygienists. The history of science is full of stories of personal animosity, spite and (now) hilariously wrong explanations. So besides being curious (as I stated in my last post), scientist also need to be critical. And first and foremost critical of their own work. If you can’t convince yourself based on your data how do you expect to convince others? Being impartial and objective is hard for everyone, but as a scientist it is even more important to not get too attached to your ideas and theories. Because they are just that until you have proof and other scientists can reproduce your results. I will also explain and discuss the peer review system in place for scientific journals which is trying to safeguard science against fraud.

But I think it is also very important that scientists adhere as strictly as possible to the scientific method, which I will discuss in my next post.

Clemens J. Heilmann

P.s.: Opinions, suggestions, theories, comments? Please let’s hear them below.

Motivation to do science

2010-11-07T16:52:00.007Z

First of all, I would like to welcome every reader to our blog. We hope we can interest you at least a little in science and make it more understandable why people in the prime of their live like to spend time day, night and weekends in labs and in front of computers instead of partying and just having a good time. But actually, to be honest we do have a good time. And here is why…

The way people get into science is very diverse but we all share on basic trait that a scientist can’t do without, curiosity. Curiosity killed the cat but luckily the cat has nine lives. This analogy is actually truer than you would think. One of the first things you have to learn to deal with in science is failure. And frustration. So if you are not curious or enthusiastic about science you probably won’t make it. One of the things I think makes a good scientist is the ability to ask the question everyone in the room is thinking about but no one dares to voice. Call that curiosity for lack of a better word.

Children are the quintessential scientists. Full of enthusiasm and an insatiable curiosity for the world that surrounds them, they go forth and explore their world. And this curiosity is the hardest thing to conserve when you get older. Other, more important things start to enter the equation of what makes our life successful (family, money, power). So science is also escapism in a way. Because despite its rigorous rules for publication and proper research, most scientists are whimsical, funny and most importantly, curious. Basically, scientists didn’t really want to grow up but still made something out of their natural strengths.

But why do we accept to bear the common failures and frustrations of daily lab work? I think the reason is that we want to understand and we love it when all parts of a puzzle come together and form a stunning no picture of the world that surrounds us. And we are the first to have a glimpse. This glimmer of knowledge is what we are after. If you look into the past, you will always see that science is the great door opener to improving the human condition. Curing numerous diseases, developing clean, sustainable sources of electricity, increasing the quality of life for everyone on this planet are some of the key challenges for humanity. Science can solve or at least help to solve most of them.

Most scientists are not Marie Curie, Robert Koch, Louis Pasteur or Leonardo da Vinci. But we all strive for that flash of genius and that brilliant deduction about the world that surrounds us. Whenever we understand something, we want more. And we never give up. We always look for the next puzzle to solve or when we solve one, we only see it as a small part of an even bigger picture.

Clemens Heilmann