Thomas A. Steitz 1940–2018

Thomas Steitz with young scientists at the Lindau Nobel Laureate Meeting 2018. Photo/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

The Council and Foundation Lindau Nobel Laureate Meetings deeply mourns the loss of laureate Thomas Steitz, who sadly passed away on 9 October 2018 at the age of 78. He received the 2009 Nobel Prize in Chemistry for his studies on ribosomes.

Steitz completed his Ph.D. in biochemistry and molecular biology at Harvard University in 1966. After research stays in Europe, he moved back to the US. He was a Sterling Professor of Molecular Biophysics and Biochemistry and Professor of Chemistry at Yale University.

Thomas Steitz participated in four Lindau Nobel Laureate Meetings, only recently in 2018. The Council and Foundation extend their deep sympathies to Thomas Steitz’ family.

2018 Nobel Prize in Chemistry

2018 Nobel Laureates Frances H. Arnold, George P. Smith and Sir Gregory P. Winter. Illustration: Niklas Elmehed. Copyright: Nobel Media AB 2018.

On Wednesday, 3 October 2018, the Royal Swedish Academy of Sciences has awarded the Nobel Prize in Chemistry 2018 to Frances H. Arnold “for the directed evolution of enzymes”  and to George P. Smith and Sir Gregory P. Winter “for the phage display of peptides and antibodies”.

Find out more about the 2018 Nobel Prize in Chemistry here.

The Power of Evolution: Nobel Prize in Chemistry 2018

Today, the Royal Swedish Academy of Sciences announced the 2018 Nobel Laureates in Chemistry. Frances H. Arnold (USA) received one half of the prize “for the directed evolution of enzymes”; the other half of the prize was awarded to George P. Smith (USA) and Sir Gregory P. Winter (UK) “for the phage display of peptides and antibodies”.

2018 Nobel Laureates Frances H. Arnold, George P. Smith and Sir Gregory P. Winter. Illustration: Niklas Elmehed. Copyright: Nobel Media AB 2018.

From the press release of the Royal Swedish Academy of Sciences:

“The power of evolution is revealed through the diversity of life. The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring the greatest benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and in some cases curemetastatic cancer.”

Read more about the 2018 Nobel Prize in Chemistry here.

Der 3D-Code des Genoms

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Der genetische Code besteht aus einer Reihe von Buchstaben, welche die Anleitungen für das normale Wachstum, die Reparatur und die routinemäßigen Abläufe in Zellen buchstabieren. Inzwischen deutet vieles darauf hin, dass die verknäuelte DNA-Struktur einen zweiten Code enthält. Möglicherweise steuern Position und Packungsdichte von Nukleinsäuren, welche Instruktionen zu einem bestimmten Zeitpunkt zugänglich und aktiv sind. Eine beeinträchtigte Genomstruktur könnte unter anderem für Krankheiten wie Krebs und Missbildungen verantwortlich sein.

Damit sie in das Innere einer Zelle passt, vollbringt die DNA eine unglaubliche akrobatische Meisterleistung: Zwei Meter Material werden in einen nur ein paar Mikrometer messenden Zellkern gepresst. Die DNA verdichtet sich eigenständig, indem sie sich zunächst um Histonproteine wickelt und so eine Nukleosomkette bildet, die wie eine Perlenschur aussieht. Anschließend wickeln sich die Nukleosomen zu Chromatinfasern auf, die sich wie Spaghetti in einem Topf verknäueln.

Zur Aufdeckung des strukturellen genetischen Codes untersuchen Forscher das Chromatin von der Nukleotidsequenz bis zur Organisation eines gesamten Genoms. Aufgrund der Entwicklung mikroskopischer Verfahren zur verbesserten visuellen Darstellung der detaillierten Chromatinstruktur – sogar in lebenden Zellen – ist man heute noch besser in der Lage, den Zusammenhang zwischen Strukturveränderungen und Genexpression bzw. Zellfunktion zu erforschen. Die heute möglichen Aufnahmen der Chromatinstruktur helfen bei der Beantwortung einiger der größten Fragen der Genombiologie.

 

Chromatinkompartimente

 Eine vorherrschende Theorie bezüglich der Chromatinstruktur besagt, dass sich Nukleosomen zu 30 nm dicken Fasern aufwickeln, die sich dann zu zunehmend größeren Strukturen zusammenlagern und schließlich Chromosomen bilden. Der Beleg hierfür sind Beobachtungen, nach denen in gereinigter Form aus Zellen gewonnene DNA und Nukleosomen 30 nm bzw. 120 nm dicke Fasern bilden.

 In der Arbeitsgruppe von Clodagh O’Shea am Salk Institute for Biological Studies fragte man sich, wie Chromatin wohl in intakten Zellen aussieht. 2017 entwickelten die Forscher ein Verfahren zur Sichtbarmachung von Chromatin in intakten menschlichen Zellen, die ruhten bzw. sich teilten. Die Forscher beschichteten die Zell-DNA mit einem Material, das Osmiumionen absorbiert, was dazu führt, dass die Nukleinsäure einen Elektronenstrahl besser streuen kann und dadurch in einer elektronenmikroskopischen Aufnahme sichtbar wird. Als Nächstes wendeten sie ein modernes elektronenmikroskopisches Verfahren an, bei dem die Proben schräg in einen Elektronenstrahl gehalten werden und das dreidimensionale Strukturinformationen liefert. Die Forscher stellten fest, dass Chromatin in Form einer semiflexiblen, 5 bis 24 nm dicken Kette vorlag, die in einigen Abschnitten der Zelle dicht und in anderen locker gepackt war.

Neues Verfahren zur dreidimensionalen Darstellung der Chromatinorganisation innerhalb eines Zellkerns (violett): das Chromatin wird mit einem Metall gussbeschichtet und elektronenmikroskopisch (EM) abgebildet. Vorderer Block: Darstellung der Chromatinorganisation; mittlerer Block: elektronenmikroskopische Aufnahme; hinterer Block: Konturlinien der Chromatindichte von gering (cyan und grün) bis hoch (orange und rot). Credit: Salk Institute

“Wir zeigen, dass Chromatin keine klaren Strukturen höherer Ordnung bilden muss, damit es in den Zellkern passt”, so O’Shea. „Es ist die Packungsdichte, die möglicherweise die Zugänglichkeit des Chromatins verändert und begrenzt, indem sie eine lokale und globale Strukturbasis für die Integration verschiedener Kombinationen von DNA-Sequenzen, Nukleosomvariationen und -modifikationen in den Nukleus zur minutiösen Feinabstimmung der funktionellen Aktivität und Zugänglichkeit unserer Genome bereitstellt.“

Neben der Packungsdichte stellt die Position eine weitere Komponente der strukturellen Organisation des Chromatins dar. Es ist bereits seit 30 Jahren bekannt, dass Chromatin Schleifen bildet und so Gene näher zu Sequenzen hinzieht, die ihre Expression regulieren. Der Biologe Job Dekker und seine Mitarbeiter von der University of Massachusetts Medical School in Worcester haben verschiedene molekularbiologische Techniken zur Identifizierung benachbarter, 200.000 bis eine Million Basen langer Chromatinabschnitte entwickelt. Bei einer dieser Techniken, dem sogenannten Hi-C, wird die Chromatinstruktur anhand ihrer Sequenz kartiert.

Bei dem Hi-C-Verfahren wird die Nukleinsäure zunächst mit nahe beieinander liegenden Chromatinabschnitten chemisch vernetzt. Anschließend wird das vernetzte Chromatin mit Hilfe von Enzymen zerschnitten und die losen Enden werden mit einem modifizierten Nukleotid markiert. Danach werden nur vernetzte Fragmente wieder miteinander verbunden. Schließlich isolieren die Forscher die Chromatinfragmente, sequenzieren sie und ordnen die Sequenzen ihrer Position im Gesamtgenom einer Zelle zu.

Im Jahr 2012 identifizierten Bing Ren und seine Mitarbeiter von der University of California, San Diego School of Medicine mittels Hi-C Chromatinregionen, die sie als topologisch assoziierte Domänen (TAD) bezeichneten. Gene in ein- und derselben TAD treten stärker miteinander in Wechselwirkung als mit Genen in anderen TAD, und Domänen, in denen eine aktive Transkription stattfindet, besetzen andere Positionen in einem Zellkern als ruhende Domänen. Veränderte Sequenzen innerhalb einer TAD können zu Krebs und Gliedmaßenfehlbildungen bei Mäusen führen.

Man geht davon aus, dass durch einen Proteinanker gezogene Chromatinschleifen die Grundeinheit einer TAD bilden. In modernen Computermodellen der Chromatinfaltung lassen sich mittels Hi-C beobachtete Wechselwirkungen des Chromatins bei der Schleifenbildung simulieren. Genomforscher sind sich jedoch nach wie vor nicht sicher, welche Proteine an der Schleifenbildung beteiligt sind. Die Beantwortung dieser Frage betrifft eine grundlegende Eigenschaft der DNA-Faltung und könnte auf einen zellulären Krankheitsmechanismus infolge von Mutationen in einem Schleifenverankerungsprotein deuten.

 

Superauflösende Mikroskopie

Moderne Methoden der optischen Mikroskopie, die auf einem Verfahren basieren, für das der Nobelpreis für Chemie 2014 verliehen wurde, liefern ebenfalls Informationen darüber, wie bis zu 100 Basen lange Chromatinregionen die Zellfunktion beeinflussen könnten. Die superauflösende Fluoreszenzmikroskopie verstärkt die Auflösung von Lichtmikroskopen, so dass die Beugungsgrenze bei mehr als 300 nm liegt. Bei dieser Technik werden fluoreszierende Moleküle mit Hilfe eines Lichtimpulses angeregt. Anschließend wird das Licht, das von nicht zentral im Anregungsstrahlengang befindlichen Molekülen emittiert wird, mittels verschiedener Kunstgriffe unterdrückt. Auf diese Weise lassen sich Aufnahmen eines einzelnen fluoreszierenden Moleküls erzeugen.

Biologische Moleküle können jedoch zahlreiche fluoreszierende Marker aufweisen, was die Lokalisation eines Einzelmoleküls erschwert. Mit Hilfe von fluoreszierenden Markern, die sich an- und ausschalten lassen, aktivieren und deaktivieren Forscher Moleküle in bestimmten Regionen zu bestimmen Zeitpunkten. Dann verbinden sie die Aufnahmen und erfassen die Positionen aller Fluoreszenzmarkierungen.

Xiaowei Zhuang und seine Mitarbeiter von der Harvard University verfolgten mittels superauflösender Mikroskopie, wie sich die Chromatinpackung basierend auf epigenetischen Modifikationen veränderte. Ihre Methode lieferte Aufnahmen im Kilo- bis Megabasen-Maßstab; diese Auflösung liegt zwischen der reiner Sequenzinformationen und der weitreichender Wechselwirkungen, die durch Hi-C darstellbar sind, wie zum Beispiel Informationen in Bezug auf Genregulation und -transkription. Dieses Verfahren eröffnet auch die Möglichkeit einer bildgebenden Darstellung von Strukturen im Nanometerbereich in lebenden Zellen.

 

Strukturwörterbuch

 Derzeit arbeiten Forscher auf der ganzen Welt an einem Wörterbuch des strukturellen genetischen Codes in Raum und Zeit und wenden dabei eine Vielzahl von Methoden zur Erfassung statischer und dynamischer Zellveränderungen an. In dem von den National Institutes of Health gegründeten 4D Nucleome Network und dem vom Europäischen Forschungsrat ins Leben gerufenen 4D Genome Project wird das Vokabular der DNA-Strukturelemente ermittelt und untersucht, welche Auswirkungen diese Struktur auf die Genexpression hat. Man ist zudem neugierig, wie sich die Chromatinstruktur im Verlauf der normalen Entwicklung sowie bei Krankheiten wie Krebs und vorzeitigem Altern verändert. Auch wenn bereits viele grundlegende Fragen geklärt werden konnten, so bleibt trotz allem noch viel zu entdecken.

Visualising the Genome’s 3D Code

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The genetic code is a sequence of letters spelling instructions for a cell’s normal growth, repair and daily housekeeping. Now, evidence is growing for a second code contained in DNA’s tangled structure. The location and packing density of nucleic acids may control which genetic instructions are accessible and active at any given time. Disrupted genome structure could contribute to diseases such as cancer and physical deformities.

To fit inside a cell, DNA performs an incredible contortionist feat, squeezing two metres of material into a nucleus only a few micrometres wide. DNA compacts itself by first wrapping around histone proteins, forming a chain of nucleosomes that looks like beads on a string. Nucleosomes then coil into chromatin fibres that loop and tangle like a bowl of noodles.

To reveal the structural genetic code, researchers examine chromatin from its sequence of nucleotides to the organisation of an entire genome. As they develop microscopy techniques to better visualise the details of chromatin structure, even in living cells, they’re better able to explore how structural changes relate to gene expression and cell function. These developing pictures of chromatin structure are providing clues to some of the largest questions in genome biology.

 

Chromatin compartments

A prevailing theory about chromatin structure is that nucleosomes coil into 30 nm fibres, which aggregate to form structures of increasing width, eventually forming chromosomes. The evidence for this comes from observing 30 nm and 120 nm wide fibres formed by DNA and nucleosomes purified from cells.

A team led by Clodagh O’Shea, at the Salk Institute for Biological Studies wondered what chromatin looked like in intact cells. In 2017, the researchers developed a method to visualise chromatin in intact human cells that were resting or dividing. The researchers coated the cells’ DNA with a material that absorbs osmium ions, enabling the nucleic acid to better scatter an electron beam and by doing so appear in an electron micrograph. Next, they used an advanced electron microscopy technique that tilts samples in an electron beam and provides structural information in 3D. The researchers noticed that chromatin formed a semi-flexible chain 5 to 24 nm wide that was densely packed in some parts of the cell and loosely packed in others.

 

New method to visualise chromatin organisation in 3D within a cell nucleus (purple): chromatin is coated with a metal cast and imaged using electron microscopy (EM). Front block: illustration of chromatin organisation; middle block: EM image; rear block: contour lines of chromatin density from sparse (cyan and green) to dense (orange and red). Credit: Salk Institute

“We show that chromatin does not need to form discrete higher-order structures to fit in the nucleus,” said O’Shea. “It’s the packing density that could change and limit the accessibility of chromatin, providing a local and global structural basis through which different combinations of DNA sequences, nucleosome variations and modifications could be integrated in the nucleus to exquisitely fine-tune the functional activity and accessibility of our genomes.”

Along with packing density, location is another component of chromatin structural organisation. Researchers have known for three decades that chromatin forms loops, drawing genes closer to sequences that regulate their expression. Biologist Job Dekker, at University of Massachusetts Medical School in Worcester, and his colleagues have developed several molecular biology-based techniques to identify neighbouring sections of chromatin 200,000 to one million bases long. One of these techniques, called Hi-C, maps chromatin structure using its sequence.

In Hi-C, researchers first chemically crosslink the nucleic acid to join portions of chromatin that are near each other. Then they use enzymes to cut the crosslinked chromatin, label the dangling ends with a modified nucleotide, and reconnect only crosslinked fragments. Finally, the researchers isolate the chromatin fragments, sequence them, and match the sequences to their position in a cell’s whole genome.

In 2012, Bing Ren, at the University of California, San Diego School of Medicine,and colleagues used Hi-C to identify regions of chromatin they called topologically associating domains (TADs). Genes within the same TAD interact with each other more than with genes in other TADs, and domains undergoing active transcription occupy different locations in a nucleus than quiet domains. Altered sequences within a TAD can lead to cancer and malformed limbs in mice.

The basic unit of a TAD is thought to be loops of chromatin pulled through a protein anchor. Advanced computer models of chromatin folding recreate chromatin interactions observed using Hi-C when they incorporate loop formation. But genome scientists still aren’t sure which proteins help form the loops. Answering that question addresses a basic property of DNA folding and could point to a cellular mechanism for disease through mutations in a loop anchor protein.

 

Super resolution microscopy

Advanced optical microscopy techniques, based on a method recognised by the 2014 Nobel Prize in Chemistry, are also providing information about how regions of chromatin tens of bases long could influence cell function. Super-resolution fluorescence microscopy enhances the resolution of light microscopes beyond the 300-nm diffraction limit. This technique uses a pulse of light to excite fluorescent molecules, and then applies various tricks to suppress light shining from those molecules not centred in the path of the excitation beam. The result is the ability to image a single fluorescent molecule.

Biological molecules, however, can carry many fluorescent labels, making it difficult to localise a single molecule. Using fluorescent labels that switch on and off, researchers activate and deactivate fluorescent molecules in specific regions at specific times. Then they stitch the images together to capture the locations of all the fluorescent tags.

Xiaowei Zhuang, at Harvard University, and colleagues used super resolution microscopy to follow how chromatin packing changed based on its epigenetic modifications. Their method provided images on a scale of kilobases to megabases, a resolution between that of pure sequence information and large-scale interactions available through Hi-C. Information about gene regulation and transcription happens on this scale. This technique also offers the potential of imaging nanometre-scale structures in live cells.

 

Structural dictionary

 Using a variety of methods to capture static and dynamic cellular changes, researchers around the world are working to write a dictionary of the structural genetic code throughout space and time. The 4D Nucleome Network, funded by the National Institutes of Health, and the 4D Genome Project, funded by the European Research Council, are identifying a vocabulary of DNA structural elements and relating how that structure impacts gene expression. They’re also curious about how chromatin structure changes over the course of normal development as well as in diseases such as cancer and premature aging. With many basic questions outstanding, much remains to be discovered along the way.

Antibiotika und multiresistente Erreger: ein erbitterter Wettlauf

Antibiotika sind ein wesentlicher Bestandteil der modernen Medizin, und zwar nicht nur zur Behandlung hartnäckiger Hals- oder Ohrenentzündungen – sie spielen auch eine wichtige Rolle bei Routineoperationen wie Kaiserschnitten und Blinddarmoperationen, ebenso im Rahmen von Chemotherapien.

Wenn heute ein Antibiotikum verschrieben wird, ist es meist ein Präparat aus dem 20. Jahrhundert. Und da „Bakterien leben wollen, aber klüger sind als wir“, wie Nobelpreisträgerin Ada Yonath so treffend bemerkt, haben viele Krankheitserreger bereits Resistenzen gegen die häufigsten Antibiotika entwickelt. Im September wandte sich deshalb die Weltgesundheitsorganisation WHO mit einem eindringlichen Appell an Regierungen und Pharmahersteller, sie sollten dringend die Ausgaben für die Antibiotikaforschung erhöhen: Es gäbe einfach zu wenig neue Mittel, an denen zurzeit geforscht würde, um die wachsende Zahl multiresistenter Keime zu bekämpfen. Jedes Jahr sterben geschätzte 700 000 Patienten an den Folgen einer Infektion mit einem solchen Keim, und diese Zahl wird eher wachsen als schrumpfen.

Allein eine Viertelmillion Todesfälle gehen auf multiresistente Tuberkulose-Erreger zurück, weshalb diese Erreger den Experten besonders viele Sorgen bereiten. Wenn man einen solchen Erreger mit den verfügbaren Mitteln besiegen möchte, muss die Therapie konsequent über bis zu 20 Monate durchgehalten werden – in ärmeren Ländern oder auch in Haftanstalten wird die Behandlung aber häufig abgebrochen. Das Ergebnis sind neue Resistenzen (siehe Grafik am Ende des Artikels).

Kopfzerbrechen bereitet den Experten auch das mulitresistente Bakterium Neisseria gonorrhoea, das die Geschlechtskrankheit Gonorrhoe verursacht. Diese Bakterien sind gramnegativ, das bedeutet, dass ihre Oberflächen keine Gram-Färbung annehmen. Diese widerspenstige Oberfläche ist auch der Hauptgrund, weshalb solche Bakterien schwer zu behandeln sind, auch ohne Resistenzen. In den letzten Monaten gab es weltweit mehrere Gonorrhoe-Ausbrüche, für die resistente Keime verantwortlich sind.

 

Antibiotikaresistenz-Tests: Ein Bakterienstamm wird in ein Kulturmedium eingebracht. Die Bakterienkultur in der linken Schale ist gegenüber allen getesteten Antibiotika empfindlich, während die Kultur in der rechten Schale nur gegenüber drei der sieben getesteten Antibiotika empfindlich ist. Foto: Dr. Graham Beards, 2011, CC BY-SA 4.0

Antibiotikaresistenz-Tests: Ein Bakterienstamm wird in ein Kulturmedium eingebracht. Die Bakterienkultur in der linken Schale ist gegenüber allen getesteten Antibiotika empfindlich, während die Kultur auf der rechten Seite nur gegenüber drei der sieben getesteten Antibiotika empfindlich ist. Foto: Dr. Graham Beards, 2011, CC BY-SA 4.0

 

Solche Ausbrüche beleuchten ein weiteres Problem: Resistente Keime reisen schnell. Ganz egal, wo auf der Erde sich die Resistenzen entwickeln, durch moderne Verkehrsmittel wie Langstreckenflüge kann sich ein resistentes Bakterium innerhalb weniger Tage weltweit verbreiten. Die WHO hat eine aktuelle Liste mit 12 resistenten Bakterienstämmen erstellt, die als besonders gefährlich gelten. Diese Liste enthält nicht nur die Gonorrhoe-Erreger, sondern auch den gefürchteten Krankenhauskeim MRSA (die Abkürzung steht für Methicillin-resistenter Staphylococcus aureus).

 

Abhilfe durch bildgebende Verfahren?

Lösungsvorschläge werden möglicherweise von unerwarteter Seite kommen, zum Beispiel von Forschern, die mit Kryo-Elektronenmikroskopie arbeiten, kurz Kryo-EM. Der Chemienobelpreis 2017 würdigt diese Entwicklung. Mit Hilfe dieser Methode erhalten die Forscher eine derart hohe Auflösung des Zellgeschehens, dass sie sogar diejenigen Proteine beobachten können, die Resistenzen gegen Antibiotika weitergeben. Kryo-EM baut auf den Erfahrungen der Kristallstrukturanalyse auf, sowie auf der Methode der klassischen Elektronenmikroskopie.

Das Beobachten von Vorgängen ist in der Wissenschaft häufig der erste Schritt zu einem tiefgreifenden Verständnis, das erklärt die große Bedeutung von bildgebenden Verfahren für die Lebenswissenschaften. Wenn nämlich die Forscher Proteine ‘sehen’ können, die Resistenzen weitergeben, dann kann dies der Startpunkt für die Entwicklung von Medikamenten sein, die dieses Geschehen unterdrücken. Nun eignet sich die Kryo-EM besonders gut für Oberflächenproteine, sie stellt also genau jene Orte gut dar, an denen Infektionen oder Gentransfers ihren Anfang nehmen.

Gleichzeitig entwickelt sich auch die optische Mikroskopie immer weiter, mittlerweile kann man ‘live’ beobachten, wie Proteine in einer Zelle synthetisiert werden. Der Chemienobelpreis 2014 war ganz der Überwindung der Auflösungsgrenze in der Lichtmikroskopie gewidmet: Stefan Hell erhielt ihn für die Entwicklung seiner STED-Mikroskopie, der amerikanische Physiker Eric Betzig entwickelte die PALM-Methode, William E. Moerner war der dritte Preisträger 2014. Kurz nachdem er den Nobelpreis erhalten hatte, erfand Hell die MINFLUX-Mikroskopie, eine Kombination aus STED und PALM. Damit kann er nun erstmals kleine Filme erstellen, die zeigen, wie Proteine tatsächlich innerhalb von Zellen gebildet werden.
Alle diese Methoden zusammen führen zu einer „Auflösungs-Revolution“, die helfen wird, neue Antibiotika zu entwickeln.

 

Chemienobelpreisträgerin Ada Yonath bei einer Diskussionsveranstaltung mit Nachwuchsforschern auf der Lindauer Nobelpreisträgertagung 2016. Yonath erforscht seit Jahren die Ribosomen resistenter Bakterien. Foto: LNLM/Christian Flemming

Chemienobelpreisträgerin Ada Yonath bei einer Diskussionsveranstaltung mit Nachwuchsforschern auf der Lindauer Nobelpreisträgertagung 2016. Yonath erforscht seit Jahren die Ribosomen resistenter Bakterien. Foto: LNLM/Christian Flemming

 

Die Nobelpreisträgerin Ada Yonath, die den Chemienobelpreis 2009 für die Struktur des Ribosoms herhalten hatte, arbeitet bereits an neuartigen Antibiotika, und zwar an solchen, die nur gegen jeweils einen bestimmten Bakterienstamm wirken sollen, das nennt man ‘speziesspezifisch’. Ihr Ansatzpunkt sind die Ribosomen, also „die zellulären Maschinen, die Gene in Proteine umsetzen“, weil viele der bekannten Antibiotika die Aktivität der Ribosomen unterbinden. Zunächst studierte sie die Ribosomen ‘guter’, also harmloser Bakterien, inzwischen arbeitet sie mit MRSA-Keimen. Würde es gelingen, auf diesem Weg einen Wirkstoff zu finden, der alle Krankheitserreger abtötet, aber alle anderen Bakterien schont, wäre nicht nur die Behandlung wesentlich verträglicher – es würden auch deutlich weniger Resistenzen entstehen, unter anderem, weil deutlich weniger Bakterien überhaupt von einem solchen Wirkstoff betroffen wären.

 

Wirkstoff wird resistenter gegen Resistenzen

Eine weitere Strategie ist, an Orten nach neuen Wirkstoffklassen zu suchen, die in der Vergangenheit wenig aussichtsreich erschienen. Am Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie in Jena wurde beispielsweise ein Stoff isoliert, der sich im Labor bereits erfolgreich bei der Bekämpfung von MRSA erwies, weshalb Closthioamid 2014 zum Leibniz-Wirkstoff des Jahres gewählt wurde. Der Wirkstoff stammt von einem anaeroben Bakterium, nämlich Clostridium cellulolyticum. Diese Kategorie ist bei der Suche nach neuen Antibiotika bislang eher vernachlässigt worden. „Durch unsere Arbeit wird klar, dass das Potential einer riesigen Organismengruppe bislang völlig übersehen wurde“, so Christian Hertweck, stellvertretender Direktor des Leibniz-Instituts und Arbeitsgruppenleiter. Erst kürzlich konnten Forscher des Imperial College London, zusammen mit einem Team der ‘London School of Hygiene and Tropical Medicine’, mulitresistente Gonorrhoe-Bakterien mit Hilfe von Closthioamid abtöten. In der Petrischale reichten bereits kleine Mengen, klinische Studien sollen folgen.

In einer weiteren Strategie versucht man, existierende Antibiotika im Labor so zu verändern, dass sie ‘resistenter’ gegen Resistenzbildung werden. So brauchten Bakterien erstaunliche 60 Jahre, um gegen das Antibiotikum Vancomycin resistent zu werden. Nun haben Forscher am Scripps Research Institut (TSRI) eine verbesserte Variante dieses Wirkstoffs entwickelt, der nun Bakterien von drei Seiten gleichzeitig angreift. Das verbesserte Mittel wurde bereits erfolgreich an Enterokokken getestet, die gegen das klassische Vancomycin resistent waren. Studienleiter Dale Boger kommentiert, dass diese TSRI-Entwicklung das erste Antbiotikum sei, dass drei unabhängige Wirkmechanismen hätte, um Bakterien auszuschalten. „Dieses Merkmal wird dazu führen, die Lebensdauer des Wirkstoffs deutlich zu verlängern“, gemeint ist die Zeitspanne, in der das Mittel erfolgreich eingesetzt werden kann. „Mikroorganismen schaffen es einfach nicht, sich gleichzeitig an drei verschiedenen Fronten zu wehren. Selbst wenn sie es schnell schaffen, einen Wirkmechanismus auszuschalten, bleiben immer noch zwei übrig, die sie schließlich abtöten werden.“

 

Resistenzen ‘springen’ von einem Erreger zum anderen

Leider sind an diesem fulminanten Wettlauf nicht nur Forscher und Erreger beteiligt – eine solche Konstellation wäre noch halbwegs überschaubar. Doch die Tatsache, dass mulitresistente Keime heute sowohl unsere Umwelt als auch unsere Nahrung besiedeln, macht die Lage erst bedrohlich. Ein Beispiel hierfür ist das Antibiotikum Colistin: Bereits in den 1950er Jahren entwickelt, wurde es nie auf breiter Front gegen Infektionen beim Menschen eingesetzt, weil es zu starke Nebenwirkungen hat. Doch in den letzten Jahren ist es genau aus diesem Grund als Reserveantibiotikum interessant geworden. Da es sich aber um einen alten Wirkstoff handelt, ist der Patentschutz lange abgelaufen, die Produktion ist also preiswert – und deshalb wird es in China in großen Mengen in der Schweinemast eingesetzt.

Wie nicht anders zu erwarten, haben sich in diesen Schweinen Colistin-resistente Bakterienstämme entwickelt, deren Entdeckung erst 2015 publiziert wurde. Diese speziellen Resistenzen haben es in sich: Weil sich die Resistenz-Gene in einem Plasmid befinden, Bakterien jedoch sehr leicht Plasmide untereinander austauschen können, sind sie somit auch ein der Lage, praktisch mühelos Resistenzen auszutauschen, auch von einem Bakterienstamm zum nächsten. Bereits 2015 wurde das verantwortliche Gen namens mcr-1 in chinesischen Supermärkten entdeckt, ebenso in vereinzelten Patientenproben von dortigen Krankenhäusern. Nur 18 Monate später konnten in einem Viertel aller Krankenhauspatienten in bestimmten Regionen Chinas nun Bakterien mit diesem Resistenz-Gen nachgewiesen werden. Das Fazit lautet: Resistenzen breiten sich mittlerweile in einem beispiellosen Tempo aus.

Ein weiteres Beispiel für die Umweltverschmutzung sind große Mengen moderner Antibiotika und Antimykotika, also Anti-Pilzmittel, die in den Abwässern indischer Pharmahersteller gefunden wurden. In warmen Abwässern finden Bakterien ideale Lebensbedingungen – und wenn es dort Antibiotika gibt, werden sie sich anpassen und Resistenzen entwickeln. Schon heute haben Indienreisende bei ihrer Rückkehr häufig mulitresistente Keime im Gepäck, von denen sie meist nichts wissen, die ihnen jedoch bei einer späteren Erkrankung zum Verhängnis werden können – oder anderen Patienten.

Der erbitterte Kampf zwischen Bakterien auf der einen und Antibiotika auf der anderen Seite tobt jetzt seit 90 Jahren, seitdem Nobelpreisträger Alexander Fleming das Penicillin entdeckte. Dieser Kampf wird in Krankenhäusern, Forschungslaboren und Arztpraxen geführt. Die erwähnten Beispiele der Schweinemastbetriebe und der Abwässer von Pharmaherstellern stellen die Verantwortlichen jedoch vor völlig neue Herausforderungen, denen mit innovativen und vielseitigen Strategien begegnet werden muss. Erst vergangene Woche traf sich eine Arbeitsgruppe der Vereinten Nationen in Berlin, um diese Fragen zu erörtern. Denn eins ist klar: Die meisten von uns leben zwar nicht an indischen Abwasserkanälen, aber die Mikroben von dort erreichen uns alle.

 

Schautafel der US-Gesundheitsbehörde CDC über die Entstehung von Resistenzen. Das Problem der verseuchten Abwässer ist hier nicht berücksichtigt. Copyright: Centers for Disease Control and Prevention, 2013 Public Domain

Schautafel der US-Gesundheitsbehörde CDC über die Entstehung von Resistenzen. Das Problem der verseuchten Abwässer ist hier allerdings nicht berücksichtigt. Copyright: Centers for Disease Control and Prevention, 2013 Public Domain

Resistant Bacteria vs. Antibiotics: A Fiercely Fought Battle

Antibiotics are an integral part of today’s medicine, not only to treat a strep throat or an ear infection – they also play a huge role in routine operations like appendecotomies or cecareans, and they are indispensable as co-treatment for many chemotherapies.

If you take an antibiotic today, it has most probably been developed and approved of in the last century. And since “bacteria want to live, and they are cleverer than us,” as Nobel laureate Ada Yonath describes them succinctly, many pathogens have become resistant to these common drugs. In September 2017, the World Health Organization (WHO) published an urgent appeal to increase funding for research into new antibiotics: not enough new drugs are in the ‘pipeline’ to combat the growing problem of multi-resistant strains. Currently, an estimated number of 700,000 patients die from infections with these strains every year – and this death toll might rise.

The WHO and other experts are especially concerned about multi-resistant tuberculosis that causes about 250,000 deaths per year, and less than half of all patients receive the necessary treatment that can take up to 20 months. The problem is that disrupted treatment inevitably leads to more resistances. Another very worrisome development is the emergence of multi-resistant Neisseria strains that cause the STD gonorrhoea. Neisseria gonorrhoeae are gram-negative bacteria, meaning that their surface is not coloured by gram staining. This resilient surface is also the reason why it is hard to treat gonorrhoea infections in the first place, even without resistances. Only this year, there have been several outbreaks of this multi-resistant variant around the world.

 

Antibiotic resistance tests: the bacteria in the culture on the left are sensitive to all seven antibiotics contained in the small white paper discs. The bacteria on the right are resistant to four of these seven antibiotics. Photo: Dr Graham Beards, 2011, CC BY-SA 4.0

Antibiotic resistance tests: the bacteria in the culture on the left are sensitive to all seven antibiotics contained in the small white paper discs. The bacteria on the right are resistant to four of these seven antibiotics. Photo: Dr Graham Beards, 2011, CC BY-SA 4.0

 

This brings us to another problem: resistant bugs travel fast. No matter where they develop, with modern travel they can spread around the world within days. The WHO also published a list with 12 pathogens that pose the greatest risks. This list includes Neisseria as well as the well-known and much-feared ‘hospital bug’ methicillin-resistant Staphylococcus aureus, or MRSA.

 

Imaging technologies help to develop new drugs

Relief from this dire situation might come from unexpected sources, like the technology honoured by the Nobel Prize in Chemistry 2017: cryo-electron microscopy, or cryo-EM. With the help of this new method, researchers can ‘see’ “proteins that confer resistance to chemotherapy and antibiotics”. This method was difficult to develop, and it leaned heavily on the experiences from X-ray crystallography and classic electron microscopy.

Often in research, being able to ‘see’ something is the first step of understanding its function, hence the strong interest in imaging technology in the life sciences: if a researcher can ‘see’ the workings of a resistance-inducing protein, he or she can start working on strategies to inhibit this process. Cryo-EM is especially good at depicting surface proteins, i.e., the location where infections or gene transfers usually start.

At the same time, optical microscopy is moving ahead as well, being able to ‘watch’ proteins being coded in living cells.  The Nobel Prize in Chemistry 2014 was dedicated to the breaking of the optical diffraction limit. Stefan Hell developed STED microscopy, American physicists Eric Betzig invented PALM microscopy, and both were awarded the Nobel Prize, together with William E. Moerner, “for the development of super-resolved fluorescence microscopy”. Shortly after receiving the most prestigious science award, Stefan Hell combined STED and PALM microscopy to develop the MINFLUX microscope: the very technology that can show proteins being coded. All these methods together will result in a “resolution revolution” that may contribute to the development of new classes of antibiotics.

 

Nobel laureate Ada Yonath during a discussion with young scientists at the 2016 Lindau Nobel Laureate Meeting. Photo: LNLMM/Christian Flemming

Nobel laureate Ada Yonath during a discussion with young scientists at the 2016 Lindau Nobel Laureate Meeting. Yonath has been studying bacterial ribosomes for many years. Photo: LNLM/Christian Flemming

Nobel Laureate Ada Yonath, who was awarded the 2009 Nobel Prize in Chemistry “for studies of the structure and function of the ribosome“ with X-ray crystallography, is currently researching species-specific antibiotics. Her starting point is that many antibiotics target bacteria’s’ ribosomes, “the universal cellular machines that translate the genetic code into proteins.” First, her team studied the inhibition of ribosome activity in eubacteria, i.e., ‘good’ bacteria. Next, she extended her studies to ribosomes from multi-resistant pathogens like MRSA. Her goal is to design species-specific drugs, meaning specific to a certain pathogen. These will minimise the harm done to the human microbiome by today’s antibiotics, resulting in a more efficient cure and a lower risk of antibiotic resistance, because fewer bacteria are affected.

 

Finding new drugs in unexpected places

Another attack strategy is to look for new antibiotic agents in places that never seemed very promising. For example, in 2010 the Leibniz Institute for Natural Product Research and Infection Biology in Jena (Germany) published a new antibiotic agent found in the soil bacterium Clostridium cellulolyticum. It belongs to the group of anearobic bacteria, a group that has long been neglected in the search for antibiotics. “Our research shows how the potential of a huge group of organisms has simply been overlooked in the past,” says Christian Hertweck, head of Biomolecular Chemistry. Just recently, scientists at the Imperial College London and the London School of Hygiene and Tropical Medicine have treated resistant Gonorrhoea bacteria with Closthioamide, the agent from Jena. They found that even small quantities were highly effective in the Petri dish; clinical trials will follow.

Yet another research strategy is to make antibiotics more ‘resistant’ to resistance formation. For instance, it has taken 60 years for bacteria to become resistant to vancomycin. Now, researchers at The Scripps Research Institute (TSRI) have successfully tested an improved version of vancomycin on vancomycin-resistant Enterococci that are on the WHO list of the most dangerous pathogenes. This improved drug attacks bacteria from three different sides. The study was led by Dale Boger, co-chair of TSRI’s department of chemistry, who said the discovery made the new version of vancomycin the first antibiotic to have three independent ‘mechanisms of action’ to kill bacteria. “This increases the durability of this antibiotic,” he said. “Organisms just can’t simultaneously work to find a way around three independent mechanisms of action. Even if they found a solution to one of those, the organisms would still be killed by the other two.”

 

Drug resistance can ‘jump’ between pathogens

Unfortunately, researchers and bacteria are not the only combatants, and this fiercly fought battle is not confined to clearly marked battlegrounds. Increasingly, multi-resistant bacteria can be found in our food, mostly due to the use of antibiotics in animal farming, and even in our natural environment. One such troubling example is Colistin, an antibiotic from the 1950s, which had never been widely used in humans due to toxic side-effects; however, in recent years it has been rediscovered as a last-resort antibiotic against multi-resistant bugs. Since it is an old drug, it’s also inexpensive and widely used – on pig farms in China.

As expected, Colistin-resistant bacteria developed in pigs, which was first discovered and published in 2015. But what makes this resistance perilous is the fact that the relevant gene is plasmid-mediated, meaning it can spread easily from one bacterium to another, possibly even from one species to another. In 2015, this resistance gene, called mcr-1, was also found in pork in Chinese supermarkets and in a few probes from hospital patients. Only 18 months later, 25 percent of hospital patients in certain areas in China tested positive for bacteria with this gene: resistances start spreading at unprecedented speeds.

Another highly disturbing example are large quantities of modern antibiotics and antimycotics found in the sewage from pharmaceutical production in India. In warm water, many bacteria find ideal conditions not only to live, but also to adapt to these novel antibiotics by quickly becoming resistant. Already travellers returning from some developing countries are considered a potential health threat, because many of them are unwitting carriers of multi-resistant pathogenes.

Since the discovery of Penicillin in 1928 by Nobel Laureate Alexander Fleming, the battle between bacteria and antibiotics is fierce and ongoing. This battle is fought in the laboratories, the hospitals and doctors’ offices all over the world, with some people seeming about as determined and creative as their opponents.

But resistance-breeding grounds like Chinese pig farms or sewage pipes from pharmaceutical companies present yet another battleground and call for a strategy that needs to be innovative as well as multifaceted. Only last week, a United Nations ad-hoc group met in Berlin to discuss these challenges. To sum it up: most of us do not live next to Indian sewer pipes, but the resistant bacteria bred there may reach us all.

 

Sign by the US Centers for Disease Control and Prevention CDC how antibiotic resistances occur - you use them and you lose them. But in this graph, large-scale pollution with resistant bacteria is not even included. Image: Centers for Disease Control and Prevention, 2013 Public Domain

Sign by the US Centers for Disease Control CDC how antibiotic resistance occurs: “you use it and you lose it”. Sewage pollution with resistant bacteria from pharmaceutical production is not included in this graph. Image: Centers for Disease Control and Prevention, 2013 Public Domain

#LiNo17 Daily Recap – Friday, 30 June

The 67th Lindau Nobel Laureate Meeting ended with the Baden-Württemberg Boat Trip to Mainau Island. It was a day full of science, discussions, joy, genuine delight and even some tears. Enjoy the highlights of the last day of #LiNo17.

 

Video of the day:

 

“I felt like I had the world in my hands.” – Young scientist Hlamulo Makelane

A definite highlight of the day were the heartfelt closing remarks made in the courtyard of Mainau Castle. You can watch the entire Farewell in our Mediatheque.

Hlamulo

Browse through our mediatheque to find all lectures, discussions and more educational videos from the Lindau Meetings.

 

Picture of the day:

Nobel Laureate Rudolph A. Marcus enjoying the Baden-Württemberg Boat Trip to Mainau Island whilst conversing with young scientists. 

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Boattrip to Mainau Island

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

For Nobel Laureate Jean-Pierre Sauvage, novelty, teamwork and adventure drove advances in synthesising molecular chains and knots. Read about his work and his advice for the young scientists.

Sauvage

Do take a look at more of our inspring blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

This is the last daily recap of the 67th Lindau Nobel Laureate Meeting. The idea behind it was to bring to you the day’s highlights in a blink of an eye. We hope you enjoyed the meeting and wish you all safe travels home.

#LiNo17 Daily Recap – Thursday, 29 June

Thursday was the last day in Lindau but not the last day of the meeting. Friday is going to take the participants to Mainau Island, so while they are enjoying their last day on the picturesque island, let’s take a look at what happened yesterday. Here are our highlights from Thursday:

 

Video of the day:

All six panelists – Nobel Laureates Sir John E. Walker and Dan Shechtman, Wiltrud Treffenfeldt (Chief Technology Officer of Dow Europe GmbH), May Shana’a (Head of Research & Developmen of Beiersdorf AG) and young scientist Thomas L. Gianetti from ETH Zurich as well as chairwoman Alaina G. Levine – have strong opinions on “Science Careers” and gave excellent advise for #LiNo17 participants.

You are welcome to browse through our mediatheque for more panel discussions, lectures and other informative videos.

 

Picture of the day:

Nobel Laureate Peter Agre’s lecture on “Aquaporin Water Channels” was not only educational, but also made the young scientists laugh. Most definitely one of the best pictures of Thursday.

67th Lindau Nobel Laureate Meeting Chemistry, 25.06.2017 - 30.06.2017, Lindau, Germany, Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings Audience in Peter Agre's lecture

For even more pictures from the Lindau Nobel Laureate Meetings, past and present, take a look at our Flickr account.

 

Blog of the day:

When Nobel Laureates come to Lindau, photographer Volker Steger presents each with a surprise task. Find out what it is and how the laureates “sketch their science”.

Sketches of Science Slider

Do take a look at more of our inspring blog posts.

 

Tweets of the day:

 

Last but not least, follow us on Twitter @lindaunobel and Instagram @lindaunobel and keep an eye out for #LiNo17

We will keep you updated on the 67th Lindau Nobel Laureate Meeting with our daily recaps. The idea behind it is to bring to you the day’s highlights in a blink of an eye. The daily recaps will feature blog posts, photos and videos from the mediatheque.

 

Julie Fenton Loves a Challenge, Regardless of Scale

Interview with #LiNo17 young scientist Julie L. Fenton

This interview is part of a series of interviews of the “Women in Research” blog that features young female scientists participating in the 67th Lindau Nobel Laureate Meeting, to increase the visibility of women in research (more information for and about women in science by “Women in Research” on Facebook and Twitter). Enjoy the interview with Julie and get inspired.

 

Julie_1

Julie L. Fenton, 25, from the United States of America is a Graduate Student & PhD Candidate in Chemistry at the Pennsylvania State University, US. She is working in inorganic/materials chemistry. Nanomaterials have garnered intense interest in the scientific community, due in part to their unique shape-, size-, and composition-dependent properties, and emerging technological applications that leverage these properties require nanomaterials with very specific architectures and well-defined characteristics. Colloidal synthetic methods are among the most effective for delivering high-quality inorganic nanomaterials with desirable properties in high yield. However, the complexities of solution-based chemistry limit the ability to predict and rationally target desired products, rendering some materials and morphologies of interest inaccessible. Her work has focused on developing new synthetic and post-synthetic modification strategies in order to produce inorganic nanomaterials with precise control over product morphology, elemental composition, and crystal structure in a variety of material systems. These advances allow them to access metastable materials, morphologic features, and/or complex heterostructures with desired physical and chemical properties, many of which are not amenable to previous synthetic methods.

 

What inspired you to pursue a career in science/chemistry?

I have always had an interest in problem solving and puzzles – I love a challenge, regardless of scale. When I came up against my first chemistry class in high school, thinking about the world on a molecular level intrigued me, and I was hooked. To me, the chemical discipline represented solving some of the most complex and intriguing problems in the world, except that the answer was previously unknown. This was exciting to me as a young person, and the passion only deepened through higher-level study of chemistry through college, and now well into graduate school.

 

Who are your role models?

I have been fortunate enough to benefit from a number of fantastic mentors and role models, scientific and otherwise, throughout my life. My first (and best) role models have been my parents. Through a strong work ethic coupled with the highest value placed on integrity and respect for others, they have demonstrated to me what success in life looks like (which is not specifically linked to career success). Though my parents, who are not scientists, don’t always understand exactly what it is that I’m doing on a day-to-day basis, they are supportive at every step, encouraging me to be the best version of myself in scientific pursuits, but reminding me that the world is larger than just science, and that it’s important to stay grounded in my personal values.

Academically, I am grateful to have benefitted from and been inspired by too many people to name in this discussion, so I will name just two: my current graduate research advisor, Dr. Raymond Schaak, and my first research advisor as an undergraduate, Dr. Richard Schaeffer. These two have been phenomenally encouraging to me, helping me to develop and to think creatively as a scientist, while giving me the space to work independently on projects that I have cared about. Beyond that, they have modelled how one can balance the demands of a career in chemistry with other priorities in life. Conversations with these two have helped me to think broadly about the world and my place in it, going far beyond the expectations I could have asked for from an academic advisor.

 

How did you get to where you are in your career path?

I grew up in rural Lancaster County, Pennsylvania, USA and did my undergraduate work in chemistry at Messiah College, a small school (~2800 undergraduates only) in Grantham, Pennsylvania, USA. During my second semester as an undergraduate, I began to do research for the first time… I was enthralled by the challenge of research on the cutting edge of science. Research gave me an opportunity to think creatively about the world and the ways in which it works, and my advisor (Richard Schaeffer) gave me ample space to explore and problem-solve independently.

I anticipate working toward developing mentoring programmes to help foster students’ interest in STEM fields at an early age

Like many aspiring U.S. scientists, I participated in a National Science Foundation Research Experience for Undergraduates (NSF REU), between my third and fourth years of college. As a student coming from a small undergraduate institution, this was my first opportunity to do research full-time, working alongside graduate students and primarily research-active faculty members. As such, this experience was amongst the most formative of my young life as a chemist, igniting a passion for academic research and scientific problem solving on the highest level that will never be quenched. Unlike most undergraduate researchers, however, my REU was conducted at the Université de Strasbourg in Strasbourg, France, affording me the unique opportunity to live and to conduct research outside of the United States, where I have lived, worked, and learned for my entire life. Even though significant language and cultural barriers existed between the French research group and myself, we forged relationships and collaborations through the common language of chemistry. This is where I first understood and appreciated the international impact that work in science can have: increasingly, we are participating in an endeavour that transcends our national and cultural boundaries, aided by the ease of communication and collaboration. It was (and still is) incredibly exciting to me to contribute, in some small way, to something much greater than myself.

These experiences propelled me into graduate school, beginning in the summer of 2014, where I have been ever since, and will continue to motivate me as I move into the next stages of my career. I’m currently working towards my Ph.D. in materials/inorganic chemistry at the Pennsylvania State University in University Park, Pennsylvania, USA under the direction of Ray Schaak.

 

What is the coolest project you have worked on and why?

I’m probably totally biased, but the coolest work that I have worked on is my current dissertation work. Although it’s really important to be able to control the way that atoms arrange themselves in solid-state materials (because the atomic arrangement, or crystal structure, dictates the properties), the typical high-temperature synthetic methods for making solid-state materials are often limited to obtaining only the most stable arrangements of atoms in a solid. By using a lower-temperature, solution-based cation exchange method, we can transform a performed material template into a material with targeted composition. Interestingly, these transformations can be accomplished with the retention of some qualities of the template material, including features of the original crystal structure, circumventing some of the primary difficulties encountered in traditional solid-state chemistry. Using this approach, we have been able to target and isolate some unusual crystal structures in a predictable fashion, which begins to point towards the ability to generalise these approaches for polymorphic structure targeting in solid-state chemistry.

I think the most exciting thing about chemistry (and science in general) is that the great breakthroughs can be serendipitous and unexpected

What’s a time you felt immense pride in yourself/your work?

In different ways, I have found pride in sharing my work with others. Outside of my lab or the community of solid-state chemists, there is something really exciting about communicating the major points of my science to non-technical audiences in a way that appeals to them (without oversimplifying the science behind it), in formal presentations and informal conversations. Additionally, I have found great satisfaction and pride in seeing some of my efforts come to fruition in published form. Getting to a paper is a grind – it represents many hours in lab and many, many failed experiments, significant data analysis and interpretation, as well as the actual time spent writing the manuscript and putting together figures and data in a way that communicates the significance more broadly. It is exhilarating to contribute to the scientific community, even in very small ways.

 

Julie_2

What is a “day in the life” of Julie like?

I’m a synthetic chemist, so the majority of my work-life time is spent in the hood or nearby in the lab, weighing powders, pipetting solvents, heating/degassing a reaction, injecting precursors or decomposition agents, or cleaning and working up reactions. I spend “down” time reading papers, chatting science with my lab mates or advisor, or getting other work done (at the beginning of my graduate career, this was class assignments or grading for my teaching assignments… lately, it’s writing!). If I’m not in the synthesis lab, you could probably find me in the Penn State Materials Characterization Lab using one of the transmission electron microscopes (TEM) to take a look at the morphology of my nanoparticle samples, to analyse their crystal structures (using selected-area electron diffraction or high-resolution TEM), or to assess their elemental composition using STEM-EDS (energy dispersive spectroscopy) mapping.

 

What are you seeking to accomplish in your career?

To merge my passion for chemistry and my desire to engage others in STEM, I plan to pursue an academic research career after completing my graduate work. As a young person, I had few female academic role models; as a professional, I anticipate working toward developing mentoring programmes to help foster students’ interest in STEM fields at an early age. I look forward to leveraging my career to help bridge the gap between technical and non-technical audiences and to increase scientific literacy at all levels of academia, politics and normal life. Thus far, I have observed and begun to appreciate the unique set of opportunities available to academic scientists: engagement with top-calibre colleagues, students and mentors, involvement with a built-in community of equally passionate researchers, opportunity to converse and collaborate across disciplines and institutions, and utilisation of cutting-edge instrumentation and laboratories. Leading scientists in top academic institutions enjoy the ideal setting for making discoveries, establishing meaningful collaborations and mentoring future generations of scientists. For an ambitious and creative scientist, academic research positions provide the latitude and flexibility to innovate, the environment to pursue individual research interests (sometimes several different ones), and the opportunity to truly impact the scientific world and the world at large.

 

What do you like to do when you’re not doing research?

I enjoy traveling to new places (or familiar ones), outdoor activities, reading, board games, and spending time with family and friends. I also make some attempts to cook, though I have found that synthetic skills in chemistry do not directly translate to cooking skills (although it feels like they should).

 

What advice do you have for other women interested in science/chemistry?

Although we live in a world of instant gratification and quick answers, progress in science is often quite slow. It requires a significant investment of time, energy and thought, and even with this discipline, projects stalling or hypotheses failing is inevitable in these disciplines. This can be discouraging to anyone, but particularly to young scientists. Eventually, progress is made: an interesting discovery, fresh eyes to interpret formerly frustrating results, or new ideas and hypotheses that can be tested and proven true, but this takes time. My advice is to keep pushing towards the goal of understanding, and to stay positive — try not to let temporary frustrations get in the way of that. I would encourage young women in particular to not be intimidated by male-dominated academic science. If you want it and are willing to work hard, you are capable of achieving every success in science.

 

In your opinion, what will be the next great breakthrough in science/chemistry?

I think the most exciting thing about chemistry (and science in general) is that the great breakthroughs can be serendipitous and unexpected – although we would like to know exactly where they will come from, we don’t and we shouldn’t expect to. As a materials chemist, however, I think some of the scientific discoveries with the potential for the greatest impact on society will come from the development of new materials. I expect that the next decade and beyond will give us numerous breakthroughs in materials for a wide variety of applications, particularly those important for solar energy harvesting, fuel cells, batteries, other electronics and beyond (perhaps for applications we haven’t even thought of yet).

We should continue to reach out to and encourage aspiring scientists as children and teens, and at the undergraduate level

What should be done to increase the number of female scientists and female professors?

This is a difficult question, and one that I think (rightly) is starting to be addressed at every level of academic training and careers. I think that we, as a community, are taking steps in the right direction towards an academy that looks more representative of broader society (including more women and other under-represented groups). While progress is good, this process will take time! 30, 40 and 50 years ago, the pool of trainees looked much different than it does today, which is still reflected in the way the academy (or even in high levels of scientific industry) looks today. I think it’s important not to do this artificially at the highest levels of science, but to build up to that slowly, over a period of time. We should continue to reach out to and encourage aspiring scientists as children and teens, and at the undergraduate level, and help to change the perception of what a scientist looks like and does. At the graduate level, mentorship is extremely important, as learning from the mistakes and triumphs of others who have gone before you is valuable for making informed decisions about your career (and basically everything else).