{"id":53304,"date":"2022-11-16T12:00:00","date_gmt":"2022-11-16T11:00:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53304"},"modified":"2022-11-16T12:38:21","modified_gmt":"2022-11-16T11:38:21","slug":"from-academia-to-industry-and-back","status":"publish","type":"embletc","link":"https:\/\/www.embl.org\/news\/embletc\/issue-99\/from-academia-to-industry-and-back\/","title":{"rendered":"From academia to industry and back"},"content":{"rendered":"\n

By Tom Furnival-Adams<\/em><\/p>\n\n\n\n

As she reflects on her long, successful career, it is clear that Sara A. Courtneidge has always been driven, primarily, by an innate compulsion to discover how things work. <\/p>\n\n\n\n

Growing up in Sussex, England, she recalls excitedly rushing to the butcher\u2019s shop on her way home one day to obtain a cow eye to dissect, having been shown the ropes by a particularly enthusiastic science teacher. She also remembers taking it upon herself to examine her family\u2019s tap water using a microscope borrowed from one of her brothers\u2019 chemistry kit. <\/p>\n\n\n\n

And while these formative experiments ensured her family always boiled their water and thoroughly washed chopping boards, they also indicated early on Courtneidge\u2019s burning curiosity about the natural world that would shape the rest of her life.<\/p>\n\n\n\n

It is this extraordinary will to examine and better understand crucial mechanisms of biology that led to her 2022 Lennart Philipson Award<\/a> recognising her major contributions to foundational and translational cancer research.<\/p>\n\n\n\n

This could be perceived as her career coming almost full circle: Philipson was the Director General who recruited Courtneidge to EMBL in 1985. \u201cI had some fantastic interactions with Lennart; he was a wonderfully supportive man. I owe a lot to him,\u201d she said.<\/p>\n\n\n\n

The chemistry of serendipity<\/strong><\/h2>\n\n\n\n

Courtneidge, who attended one of Britain\u2018s first comprehensive schools, attributes much of her early success to serendipity. She considers it a stroke of luck that she was taught by a PhD-level chemistry teacher, and was one of a handful of students in her year encouraged and supported to attend university.  \u201cMy life has just been these series of fortuitous things,\u201d she said.<\/p>\n\n\n\n

In 1972, she went to the University of Leeds, having \u201cannounced\u201d that she intended to do so to parents who were both slightly bemused by, and extremely supportive of, their daughter\u2019s boldness. She was only the second member of her family to attend university and believes that her undergraduate degree in biochemistry set her up for the rest of her career. \u201cIt was a really good basis for everything we understand about modern molecular biology now,\u201d she said.<\/p>\n\n\n\n

Her PhD took her to the now-defunct National Institute for Medical Research in Mill Hill, London, where she specialised in virology and immunology. There she first encountered the role of T cells in recognising virus infection. <\/p>\n\n\n\n

\u201cI was working within two labs, one led by an immunologist, and the other led by a virologist, using influenza virus genetics to study how the T cells interact with viruses. It’s been interesting helping my friends and colleagues understand pandemics because we had a lot of conversations in my lab about pandemics and how you track them,\u201d Courtneidge recalled.<\/p>\n\n\n\n

Courtneidge would have likely have continued down that path if not for one of her PhD advisors, the virologist Sir John Skehel, intervening.  \u201cJohn said, you shouldn’t do the same thing for your postdoc that you did for your PhD,\u201d she recounted. \u201cThis is a time to broaden your horizons.\u201d<\/p>\n\n\n\n

Courtneidge began spending more time in the library, consciously following new, different trails of curiosity. She and Skehel discussed various scientific ideas at the lab bench all day long. That\u2019s how she settled upon cancer virus research.<\/p>\n\n\n\n

With Skehel\u2019s endorsement, Courtneidge became interested in the recently discovered novel retroviruses, and he helped her decide to pursue this in one of the labs on the US West Coast. Having never flown before and having only been abroad once, she found herself on a plane bound for University of California, San Francisco to work with the respected microbiologist J. Michael Bishop.<\/p>\n\n\n\n

Bishop was later awarded the 1989 Nobel Prize in Physiology or Medicine with Harold Varmus, with whom he discovered the first human oncogene, c-src<\/em> , which they were using to study cancer. Meanwhile, colleagues in the lab had just determined the protein that this particular oncogene made, c-Src. It had also just been discovered in another lab that the Src protein was a kinase \u2013 an enzyme that adds phosphate groups onto other proteins.<\/p>\n\n\n\n

Courtneidge found she was one of the few scientists in the lab familiar with biochemistry and how to handle proteins. \u201cPeople were saying, \u2018Gosh, I wish there was a way we could find out where this protein is in the cell and what it does.\u2019 And I said \u2018this is something I know how to do\u2019,\u201d she said.<\/p>\n\n\n\n

\u201cIt was an amazing time to work on oncogenes,\u201d Courtneidge said. \u201cNow we had this single protein that could turn a normal cell into a cancer cell. There was this push to work out how it does that. That\u2019s when I started working on Src in the lab.\u201d<\/p>\n\n\n\n

\"\"
Sara Courtneidge in 1985. Credit: Sara A. Courtneidge<\/figcaption><\/figure>\n\n\n\n

After her PhD, Courtneidge returned to the National Institute for Medical Research. It had recently been discovered by scientists at the Salk Institute that a DNA tumour virus oncogene called middle T had some kinase activity associated with it \u2013 but they couldn’t show that it was a kinase itself. Once again, she possessed the skills and knowledge in the right place at the right time: \u201cI had all the tools from working on Src and Alan Smith\u2019s lab at NIMR had all the tools for working on polyomavirus and the middle T oncogene.\u201d<\/p>\n\n\n\n

Courtneidge collaborated with Smith and discovered that the Src protein binds to middle T protein produced by DNA tumour viruses when they infect the cell. That switches on Src activity that causes cancer. This major finding united two different research fields and paved the way for further developments.<\/p>\n\n\n\n

\u201cGenerally, most DNA viruses just take the brake away [from cell cycle regulation). But the polyomavirus both takes the brakes away and expresses a very potent tumour virus oncogene which activates the accelerator. It was pretty clear at the outset that that was a fundamental reuniting of the tumour virus fields, which were split for a while, and it started a lot of other research,\u201d said Courtneidge.<\/p>\n\n\n\n

Becoming EMBL\u2019s first female senior scientist<\/strong><\/h2>\n\n\n\n

In 1985, Courtneidge brought this research to EMBL, where she was, for a long period, the only female group leader. She later became EMBL\u2019s first female senior scientist. <\/p>\n\n\n\n

\u201cIt’s an intolerable burden on women to be the one example of a woman in a room because then, if you give a bad talk, it is generalised into \u2018women give bad talks\u2019,\u201d she said.  \u201cIf your paper isn’t well received, it\u2019s \u2018women’s papers are inferior\u2019.\u201d Courtneidge has been a passionate and active spokesperson for gender equality in science throughout her career, believing better representation is key. <\/p>\n\n\n\n

Courtneidge credits EMBL\u2019s multicultural environment for her insights into the many ways to approach research questions. She also recalls a \u201ccollaborative spirit and an open mindedness\u201d that fostered trust between colleagues and prioritised idea sharing above competition.<\/p>\n\n\n\n

 \u201cI have never had more than 10 people in my lab since EMBL,\u201d she said of the impacts EMBL has had on her approach. \u201cHaving a smaller lab helps collaboration; it’s not just about how many papers you produce and doing your own thing.\u201d<\/p>\n\n\n\n

\"\"
Courtneidge group members in the late 1980s. Top row, left to right: Stefano Fumagalli, Leonardo Brizuela, Manfred Koegl, Thorsten Erpen, Geraldine Twamleyl-Stein. Bottom row, left to right: Gema Alonso, Angelika Heber, Serge Roche, Margaret Jones. Credit: Sara A. Courtneidge<\/figcaption><\/figure>\n\n\n\n

Translational research and industry beckon<\/strong><\/h2>\n\n\n\n

After nearly 10 years in Heidelberg, industry called.  <\/p>\n\n\n\n

\u201cAt EMBL, we were publishing great papers, left, right and centre with wonderful people in my lab,\u201d she said. \u201cBut I reached a point where I asked, \u2018Is there more\u2019?\u201d<\/p>\n\n\n\n

An opportunity in San Francisco caught her attention.<\/p>\n\n\n\n

\u201cIf you want to develop treatments for people based on all the amazing scientific discoveries that were happening in the oncogene field, you had to apply that in some way. And I just thought: \u2018I need to put my money where my mouth is,\u2019\u201d she said.<\/p>\n\n\n\n

Courtneidge joined SUGEN Inc. as Head of Research in 1994, where she guided novel kinase discovery and validation efforts in oncology, and developed the company\u2019s research operations. Her own research had to move to the backburner while she focused on the company\u2019s priorities, but Courtneidge has no regrets. She believes scientists should gain experience in both translational and fundamental research. <\/p>\n\n\n\n

\u201cHow are you going to sell your research to a company if you haven\u2019t thought through what they\u2019d be interested in? What are the potential risks? What are the economics?\u201d she said.<\/p>\n\n\n\n

Realising the day-to-day demands of business administration were leaving her little time for the scientific research she loved, Courtneidge ultimately returned to academia in 2001 to establish a lab at the Van Andel Research Institute in Grand Rapids, Michigan, focusing on applying fundamental research on how cancer cells move to identifying ways to interfere with metastasis.<\/p>\n\n\n\n

She has since served as a professor and Director of the Tumor Microenvironment and Metastasis Program, and Director of Academic Affairs, at the Sanford Burnham Medical Research Institute, before joining Oregon Health and Science University in 2014, where she worked as an Associate Director of Translational Sciences for the Knight Cancer Institute.<\/p>\n\n\n\n

Courtneidge\u2019s work over a number of decades has significantly contributed to understanding oncogene transformation, regulation, substrate selection, and function.<\/p>\n\n\n\n

But Courtneidge is characteristically humble about her legacy. Instead of awards or accolades, she focuses on discoveries and new knowledge. <\/p>\n\n\n\n

\u201cI want to leave a body of work and a toolbox for others to carry it forward,\u201d she reflected. \u201cI stood on the shoulders of giants, and I want everybody to keep climbing upwards towards better understanding\u201d.<\/p>\n","protected":false},"excerpt":{"rendered":"

Sara A. Courtneidge, recipient of the 2022 Lennart Philipson Award, reflects on the fundamental and translational research aspects of her career in cancer research<\/p>\n","protected":false},"author":16,"featured_media":54024,"parent":0,"menu_order":0,"template":"","tags":[],"class_list":["post-53304","embletc","type-embletc","status-publish","has-post-thumbnail","hentry"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"

Sara A. Courtneidge, recipient of the 2022 Lennart Philipson Award, reflects on the fundamental and translational research aspects of her career in cancer research<\/p>\n","related_links":[{"link_description":"2022 EMBL Alumni Awards Winners announced","link_url":"https:\/\/www.embl.org\/news\/alumni\/2022-embl-alumni-award-winners-announced\/"},{"link_description":"EMBL Alumni Relations programme","link_url":"https:\/\/www.embl.org\/about\/info\/alumni\/"}],"source_article":false,"in_this_article":false,"press_contact":"None","article_translations":false,"languages":"","embletc_issue":[{"ID":53290,"post_author":"124","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"","post_title":"Issue 99","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"issue-99","to_ping":"","pinged":"","post_modified":"2022-11-17 11:34:48","post_modified_gmt":"2022-11-17 10:34:48","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc-issue&p=53290","menu_order":0,"post_type":"embletc-issue","post_mime_type":"","comment_count":"0","filter":"raw"}],"embletc_in_this_issue":[{"ID":53302,"post_author":"100","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

The sun sets on a Thursday evening in Casalvecchio di Puglia, a remote village in rural southern Italy. Amidst a pastoral setting of vineyards, wheat fields, and olive groves, a young girl convinces her parents and siblings to watch another episode of \u201cSuperquark\u201d, a science show aired throughout Italy, but perhaps watched in few other households in this village of approximately 2,000 residents. <\/p>\n\n\n\n

Superquark \u2013 a science show that debuted in the \u201890s in Italy \u2013 showcases a variety of science stories and profiles of scientists.  And for Maria Antonietta Tosches, it began a lifelong passion. <\/p>\n\n\n\n

Her interest piqued by scientific discoveries featured in every episode, Tosches ultimately went on to pursue the principles that drive evolution of neuron types and brain circuits. Her foray began with frogs, then moved onto Platynereis<\/em> worms, then turtles and lizards, and now, Spanish ribbed newts (Pleurodeles<\/em>). At Columbia University, Tosches is exploring newts\u2019 simple neural networks as models for more complicated ones.<\/p>\n\n\n\n

Tosches\u2019 research \u2013 recognised with EMBL\u2019s 2022 John Kendrew Award for original contributions to the field of brain evolution \u2014 is testament to her commitment to a calling very different from her parents, who are farmers still in Italy. But it is also a demonstration of the work ethic and values she has held dear throughout her personal and professional life.<\/p>\n\n\n\n

\u201cMy parents put 100 % into everything they do,\u201d Tosches said. \u201cIt\u2019s from them that I learned to strive for excellence. I see this in myself when I am running my projects, setting priorities \u2013 trying to do the best things possible in the best possible way. It\u2019s been 20 years since I left my village, and I would never have imagined this kind of work for myself then.\u201d<\/p>\n\n\n\n

From worms to turtles to newts<\/strong><\/h2>\n\n\n\n

Even before Tosches earned her PhD at EMBL, she was studying the development of retinas in frogs.  She joined Detlev Arendt\u2019s group at EMBL Heidelberg where his group was exploring the evolution of neurons, using the Platynereis<\/em> worm\u2019s nervous system as a model organism. <\/p>\n\n\n\n

At EMBL, Tosches took up work that Arendt had started as a postdoc when he discovered photoreceptor cells similar to those found in retinas, but in the middle of a Platynereis <\/em>larva\u2019s brain. She wanted to understand why they were there. Through a series of experiments, she discovered these cells are part of a larger group that produces melatonin, a chemical that essentially helps tell a body when it\u2019s time to sleep. In the case of the worm larvae, swimming and dispersing in the sea, the melatonin is used by these photoreceptor cells to sense when it is night or day so the worm larvae\u2019s swimming circuits can slow down during night.  <\/p>\n\n\n\n

\u201cThis work showed how the same molecule is used in animals that diverged from human\u2019s evolutionary path 600 million years ago, to do something very similar \u2013 controlling circadian rhythms of locomotion,\u201d Tosches explained. \u201cThe light-dependent control of locomotion is something that has existed since the beginning of the evolution of animal nervous systems. Other researchers discovered that even jellyfish sleep, and melatonin modulates or is involved in sleep mechanisms. This link between sleep and melatonin is something very, very ancient in animals.\u201d<\/p>\n\n\n\n

In 2014, Tosches joined the group of Gilles Laurent at the Max Planck Institute for Brain Research as a postdoc. There, she used a single-cell approach to study the evolution of cerebral cortices in turtles and lizards, choosing them because they have the simplest cerebral cortex. <\/p>\n\n\n\n

\u201cFor many decades, scientists have been comparing the brains of frogs, fish, turtles, and of course, mammals, and describing the neuroanatomy of these brains,\u201d Tosches said. \u201cBut what's still obscure is how the differences<\/em> between these different vertebrate brains came about.\u201d<\/p>\n\n\n\n

\"Photo
In five to 10 years, the EMBL alumna hopes the Spanish ribbed newt, Pleurodeles waltl<\/em> will help her to create a complete, cell-by-cell description of how neural circuits are assembled and organised in a vertebrate brain. Credit: Wenze Li<\/figcaption><\/figure>\n\n\n\n

Additionally, Tosches has been interested in learning more about the cognitive capacities of vertebrates besides what has been gleaned from mice, primates, and humans. <\/p>\n\n\n\n

\u201cAbout 320 million years ago, one vertebrate evolutionary line led to us mammals, and another led to reptiles and birds. And in these passing years, lots of changes happened,\u201d she said. \u201cEventually, mammals and birds acquired very high cognitive abilities independently. Birds are incredibly smart and have been studied more than other vertebrates with simpler cognition, which are not understood at all yet.\u201d<\/p>\n\n\n\n

Since 2019, she has led her own research lab at Columbia University. With newts, Tosches uses genetic, genomic, developmental, and neurobiological approaches to investigate the evolution of brain cell types and neural circuits in the vertebrate brain.<\/p>\n\n\n\n

\u201cWe are trying to understand whether salamanders can use landmarks to understand their location,\u201d she explained. \u201cA part of the brain involved in navigation, the hippocampus, has an innate ability to know where you are in space. We found that cell types there that help make this happen also exist in other species.\u201d<\/p>\n\n\n\n

In early September, her research group and collaborators published a paper in Science<\/em><\/a> exploring the similarities and differences of neuron types in the forebrains of salamanders, turtles, lizards, and mice.<\/p>\n\n\n\n

Why evolutionary neuroscience is important<\/strong><\/h2>\n\n\n\n

\u201cI am driven by curiosity,\u201d Tosches said, talking about the future of her research.  <\/p>\n\n\n\n

In five to 10 years, the EMBL alumna hopes to have created a complete, cell-by-cell description of how neural circuits are assembled and organised in a vertebrate brain. It\u2019s a \u2018dream that drives\u2019 her to think about her lesser-known Spanish ribbed newt Pleurodeles waltl <\/em>ultimately <\/em>being recognised as a model organism in much the same way that C. elegans<\/em> is extolled for its role in understanding neural circuitry.<\/p>\n\n\n\n

And in the world of fundamental scientific research, that\u2019s a very big deal.<\/p>\n\n\n\n

\u201cIf we look back at history, all the major breakthroughs in biology \u2013 and in science in general \u2013 came not because someone anticipated or planned for the societal impact or the impact on human health,\u201d she said. \u201cThat\u2019s the beauty of fundamental research. At the time many of these kinds of discoveries are made, nobody \u2013 not even the person who makes the discovery \u2013 is really aware of the influence they may have in future scientists\u2019 work or how the science can change how we think about and do things.\u201d<\/p>\n\n\n\n

Being \u2018fearless about your science\u2019<\/strong><\/h2>\n\n\n\n

Tosches\u2019 determination to reach this goal is quite evident. Her voice only grows stronger as she shares more details from her current work.  However, she is quick to add \u2013 more than once \u2013 that this drive not only comes from her parents but a culture of risk taking at EMBL.<\/p>\n\n\n\n

\u201cWhat did I learn during my time at EMBL? Not to be afraid of trying new things,\u201d she said. \u201cYou are surrounded by people doing amazing science in so many different fields; it's not like other institutes.  The environment encourages you to talk to others even about things you yourself barely understand\u2026 you learn from each other.\u201d<\/p>\n\n\n\n

She speaks of this experience as uniquely motivating, teaching her to \u2018dream big\u2019 and \u2018try new things\u2019.  And her example of living this mantra comes in her own postdoc experience following EMBL.  Upon learning of new sequencing technology available that could process thousands of cells at a time, she changed research direction, abandoning her original postdoc project to focus on a transcriptomics single-cell approach, finding herself ultimately \u2018more satisfied\u2019 in the new undertaking.<\/p>\n\n\n\n

\u201cEMBL is very special, and consequently it has aspects impossible to replicate in a single research lab,\u201d Tosches said. \u201cHowever, what I am passing down to my students and postdocs is the idea of being fearless about the science they're doing. We try new things every day because we're working on a new system, a new animal, a new model. It\u2019s important to be positive \u2013 with the attitude of open-minded explorers who seize on new, unplanned opportunities and even find unexpected results.\u201d<\/p>\n","post_title":"Studying brain evolution: from worms to newts","post_excerpt":"Newts act as model organisms for Maria Tosches, winner of the 2022 John Kendrew Award, to further explore the cellular makeup of vertebrate brains.\n","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"studying-brain-evolution-from-worms-to-newts","to_ping":"","pinged":"","post_modified":"2022-11-18 11:12:17","post_modified_gmt":"2022-11-18 10:12:17","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53302","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":53296,"post_author":"100","post_date":"2022-11-16 12:00:00","post_date_gmt":"2022-11-16 11:00:00","post_content":"\n

\"\"
Lautaro Gandara, a postdoc in EMBL\u2019s Crocker and Alexandrov groups, spends a good deal of time in Room 611, working with fruit flies to methodically discern the impacts of different pesticide ingredients upon them. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

It\u2019s a long day in room 611 with only fruit fly larvae for company \u2013 some no longer even alive. A young postdoc quickly transfers fruit fly larvae from small vials to Petri dishes with a fine-tipped paint brush. He has decided it\u2019s the gentlest process to nudge them onto the Petri dishes where he can capture their behaviour after they\u2019ve been growing in a nutrient-rich and possibly also chemical-infused medium. <\/p>\n\n\n\n

A video camera records the larvae\u2019s behaviour upon entering the Petri dish. Placed in this \u2018new world\u2019, some immediately scatter this way and that. To the untrained eye, it would seem quite random. But to Lautaro Gandara, a postdoc in EMBL\u2019s Crocker and Alexandrov groups funded by the EMBL EIPOD postdoc programme<\/a>, it has proven to be much more. He spends the next 10 days quantifying the recorded observations, measuring the stops and starts, distance gained, and other variables to yield behavioural and developmental data about the larvae.<\/p>\n\n\n\n

Such is the life of a molecular biologist investigating the effect of agricultural chemicals on a quick-developing organism \u2013 one that is potentially representative of the long-term impacts of pesticide use on living ecosystems.<\/p>\n\n\n\n

Gandara is but one of several researchers at EMBL whose work has intertwined in myriad ways to bring molecular biology insights into understanding the impacts of pesticides, their degradation, and ways to accelerate that degradation. <\/p>\n\n\n\n

EMBL\u2019s new programme, \u2018Molecules to Ecosystems<\/a>, applies some of EMBL\u2019s established approaches for studying molecular and cellular biology to better understand the environment. It is multidisciplinary. And it\u2019s so collaborative it\u2019s hard to see the organisational lines that divide EMBL\u2019s groups and units;  scientists converge to work toward multi-pronged, overlapping research goals within a new transversal theme of planetary biology<\/a>. <\/p>\n\n\n\n

This kind of fundamental research can inform approaches to pollution clean-up and potentially guide a new generation of agro-chemicals \u2013 chemicals that would still be potent enough for their intended objectives, but able to quickly degrade and disappear.<\/p>\n\n\n\n

A library that will keep on giving<\/strong><\/h2>\n\n\n\n

If you ask Michael Zimmermann how his research group began its work with pesticides, he talks about building a library \u2013 a library of chemicals contained in pesticides new and old that can still be found in our environment. <\/p>\n\n\n\n

\"\"
This year, Richard Jacoby (left) and Michael Zimmermann (right) worked with the Swiss water research institute, Eawag to coordinate several field campaigns to look at how biopollutants affect river ecosystems downstream.<\/figcaption><\/figure>\n\n\n\n

A group leader in EMBL\u2019s Structural and Computational Biology unit<\/a>, Zimmermann has been known for his work on the human gut microbiome. As he describes this foray into pesticides, he compares this newest challenge to deciphering how gut bacteria interact with foods and drugs and what that means to a wider collection of systems. Scientists can pinpoint genes within gut bacteria that can chemically modify drugs into metabolites. The same is true for chemicals eliminating weeds, crop pests, mould, and fungi. Once again, microbes can help degrade the chemicals.<\/p>\n\n\n\n

\u201cWe\u2019ve known for decades that bacteria absorb and convert xenobiotics \u2013 chemical substances that are foreign to animal life,\u201d Zimmermann said. \u201cI\u2019m pretty convinced we can apply the same molecular approaches we\u2019ve been using on human-associated bacteria to environmental bacteria. And again, we want to know not just which bacteria do this, but also which gene is responsible for the work.\u201d<\/p>\n\n\n\n

He began this quest by looking for a library of chemicals that his group could pair up with microbes reputed to be chemical killers. The library didn\u2019t exist. So, he and his group talked to various chemical manufacturers. As a result, he approached EMBL's Environmental Research Initiative (ERI)<\/a> for funding that comes from private citizens and Friends of EMBL<\/a>. By 2021 -- thanks to this ERI support -- EMBL had its own library of more than 1,000 chemicals found in pesticides plus the means to recruit a fellow to assist with a bigger project. EMBL\u2019s Chemical Biology Core Facility<\/a>, which already had a drug library of several thousand drug compounds, now stores the chemicals in a multi-well format readily usable for screens at large scale.<\/p>\n\n\n\n

The other half of this equation was, in fact, identifying microbes that could degrade or chemically modify pesticides. Richard Jacoby, became the ARISE research fellow<\/a> to work between the Zimmermann group and EMBL\u2019s Chemical Core Facility, scrutinising scientific literature, identifying approximately 100 environmental microbe candidates that he narrowed down to 30 to represent microbes found in nature.\u00a0<\/p>\n\n\n\n

\u201cWith the pollutants in the environment, we know they degrade and at different rates,\u201d Jacoby said. \u201cThe knowledge gap we want to fill comes from asking \u2018what controls that rate of degradation?\u2019 A lot of the time it\u2019s microbial metabolism. Microbes may break down one chemical while others are more recalcitrant. If we can find which microbe strains break down which chemicals, we can better predict how long a chemical will persist in the environment.\u201d<\/p>\n\n\n\n

To this end, an important part of Jacoby\u2019s work involves a mass spectrometer, which is able to identify the individual components of a given substance by their molecular mass or weight.<\/p>\n\n\n\n

\u201cI culture microbes. I inoculate them with pesticides. And then I use a mass spectrometer to detect whether the microbe has degraded that pesticide,\u201d Jacoby said. \u201cIf it has, I look for what new \u2018transformation products\u2019 have been produced and the effect they could have on ecosystems.\u201d <\/p>\n\n\n\n

From this point on, Zimmermann\u2019s team looks more closely at the bacteria most effective at aiding this degradation. They chop up its genome into small pieces of DNA and clone it into the laboratory bacterium E. coli<\/em>, and look for clones which now take on the same metabolic function of degrading pesticides as the original bacteria.  When they do this with 50 thousand clones and screen them with mass spectrometry, they can identify which particular piece of DNA holds the genes that can degrade pesticides. <\/p>\n\n\n\n

\"\"
In August 2022, EMBL scientists visited Iceland for a final pilot expedition before the launch of EMBL\u2019s \u2018Traversing European Coastlines\u2019 (TREC) project in 2023. Richard Jacoby worked with Joanna Zukowska and Kiley Seitz to collect soil samples from an Icelandic coastline \u2013 samples that will also be reviewed with mass spectrometry. Credit: Joanna Zukowska\/EMBL<\/figcaption><\/figure>\n\n\n\n

But this research only represents a part of a fundamental research picture. The Zimmermann group is beginning and planning other projects that go out into the environment to literally \u2018ground truth\u2019 their work, looking for the same microbial signatures and patterns in soil sediments and waterways to verify their lab findings. <\/p>\n\n\n\n

The intersection of fruit flies and pesticides<\/strong><\/h2>\n\n\n\n

It\u2019s been a few years and \u2018several cups of coffee\u2019 since Zimmermann and Justin Crocker, another group leader but in EMBL\u2019s Developmental Biology unit<\/a>, first chatted during a conference break about the usefulness of having a pesticide library. This seemingly modest encounter ignited the spark that has built such a library and given it increasing purpose.<\/p>\n\n\n\n

It is brightly lit in Crocker\u2019s lab on a sunny summer day in Germany, and there is an air of purpose and energy, radiating from Crocker himself. Zimmermann \u2013 as well as everyone interviewed for this story \u2013 convey this same positive vibe. Their myriad approaches complement one another, and despite tedious parts in the process \u2013 babysitting a mass spectrometer or systematically observing day-to-day changes in fruit fly larvae \u2013 it\u2019s clear the involved researchers are excited about what their work will tell them and how it fits into understanding pesticides better.<\/p>\n\n\n\n

The researchers in Crocker\u2019s lab work with a model organism \u2013 fruit flies. <\/p>\n\n\n\n

\"\"
Lautaro Gandara and Justin Crocker stand in the room where fruit flies are cared for during their involvement in research at EMBL Heidelberg. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

EMBL has a history with fruit flies. Christiane N\u00fcsslein-Volhard and Erich Wieschaus were EMBL\u2019s first researchers to be awarded a Nobel Prize in Medicine. In 1995, they were recognised for conducting the first systematic genetic analysis of fruit fly embryonic development, having identified genes responsible for the body plan of the insect embryos.<\/p>\n\n\n\n

\u201cUsing fruit flies, they looked at what you can learn when you break down a system into its barest parts,\u201d Crocker explained. \u201cWe have this beautiful groundwork done here at EMBL. We\u2019re now building on that to look at the whole system \u2013 essentially, putting it back together.\u201d<\/p>\n\n\n\n

With their simple body plan and quick growth, fruit flies can quickly add to the body of knowledge that EMBL\u2019s pesticide library affords. Crocker brought with him high-throughput approaches for doing this kind of work from his own postdoc experience at Howard Hughes Medical Institutes\u2019 Janelia Research Campus in the US. <\/p>\n\n\n\n

When Gandara isn\u2019t gathering data in room 611 or in the \u2018Fly Room\u2019 studying adult fruit flies, he is in Crocker\u2019s lab. He follows each generation of fruit flies from larva to adulthood to track various chemicals\u2019 effects on growth and development.<\/p>\n\n\n\n

The fruit flies he observed on the Petri dishes \u2013 bending, rolling, stopping, starting \u2013 are moved to bigger vials to observe daily until they reach adulthood \u2013 approximately 10 days. Two incubation rooms have been set up \u2013 each with different temperatures to control the speed of the fruit fly life cycle. Vials reside within both, each filled with a cornmeal-based medium cushioning and nourishing the flies until maturity. So far, Gandara has collected data on acute toxicity, impact of chemicals on fruit fly activity levels, and survival rates. <\/p>\n\n\n\n

Additionally, the Crocker group has \u2018germ-free\u2019 fruit flies they use in a \u2018gnotobiotic\u2019 environment \u2013 essentially a completely sterile environment where the only microbes present are the ones the researchers introduce. By isolating microbes and fruitflies in this way, they gain control of microbiome variables and can see the impact they have on the presence of pesticides in the fruit flies\u2019 microbiomes.<\/p>\n\n\n\n

\u201cUltimately, we\u2019ll have three complete datasets for the chemicals,\u201d Gandara said. \u201cThese datasets will inform us about the effects of these chemicals on normal fruit flies, germ-free flies, and bacterial microbes isolated directly from the flies\u2019 guts.\u201d<\/p>\n\n\n\n

\u201cBy looking at how pesticides affect the insect microbiome, we are filling a major knowledge gap,\u201d Jacoby said. \u201cMost work on insect pesticide toxicology has ignored the microbiome. This could provide a wealth of new information about how pesticides affect this host-microbe system.\u201d<\/p>\n\n\n\n

But Gandara\u2019s work doesn\u2019t end there. His position at EMBL crosses unit lines, and his next role in this research involves mass spectrometry and metabolomics, through EMBL\u2019s Alexandrov group.<\/p>\n\n\n\n

Nature vs. nurture and the role of metabolomics<\/strong><\/h2>\n\n\n\n

Metabolomics studies small molecules commonly known as metabolites, products of metabolism that fill and fuel all cells, biofluids, tissues, and organs. Because metabolites are influenced by both genetic and environmental factors, they are able to indicate individual cells\u2019 underlying biochemical activity and their current state or status. Researchers use mass spectrometry to suss out this information.<\/p>\n\n\n\n

\n
\"\"<\/figure>\n\n\n\n
\"\"<\/figure>\n
Lautaro Gandara and Mans Olof Ekelof conduct metabolomics studies to produce a deeper phenotypic analysis for understanding pesticide impacts. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

In the case of fruit flies\u2019 response to myriad chemicals, Theodore Alexandrov, an EMBL team leader in EMBL\u2019s Structural and Computational Biology unit, had already been working with the Crocker Group prior to the pesticide library.<\/p>\n\n\n\n

\u201cWe considered what would be a good way to profile molecular changes caused by environmental stimuli,\u201d Alexandrov said. \u201cPesticides are just one such stimuli. It could just as easily have been temperature or any other environmental factor.\u201d<\/p>\n\n\n\n

Gandara works with Mans Olof Ekelof, an Imaging Mass Spectrometrist in the Alexandrov group, to produce a deeper phenotypic analysis that metabolomics affords. By placing larvae onto glass slides, scanning them with a laser that desorbs or releases amino acids, carbohydrates, and lipids, they can identify and measure spatial distributions of metabolites within the larvae. In this way, Ekelof\u2019s mass spectrometry data is able to confirm Gandara\u2019s biological observations.<\/p>\n\n\n\n

In the coming months, Gandara and Ekelof will leverage this cutting-edge technology to study metabolic changes triggered by different agrochemicals. By doing so, they hope to provide a comprehensive view \u2013 encompassing development, behaviour, and metabolism \u2013 of how organisms deal with stressful environmental conditions. <\/p>\n\n\n\n

The future<\/strong><\/h2>\n\n\n\n
\"\"
Quince fruit in EMBL Heidelberg. Credit: Kinga Lubowiecka\/EMBL<\/figcaption><\/figure>\n\n\n\n

Right now, these research groups are still compiling data. That doesn\u2019t stop them from thinking about follow-on projects. The Crocker group looks to a time when they can collect fruit flies from around the world to further understand the natural biomes they inhabit. <\/p>\n\n\n\n

The Zimmermann group has just recently become involved with Eawag, a leading water research institute in Zurich. With funding from the Swiss National Science Foundation and the German Research Foundation, they coordinated several field campaigns this year to look at how biopollutants affect the river ecosystem downstream. Targeting six wastewater treatment facilities in Switzerland, they are just beginning to look at the microbiomes upstream and downstream from these facilities to observe microbes in action in the real world. <\/p>\n\n\n\n

Additionally, other EMBL researchers are engaged in pesticide research projects unrelated to the library at this point. <\/p>\n\n\n\n

Recently, <\/a>ERI announced that their latest grant would support the Pepperkok team as it explores how microbial mats in the ocean break down chemical pollutants using spatial-omics. Once again, <\/a>Friends of EMBL and other citizens provided this new funding.<\/p>\n\n\n\n

Members of the Bork group are also hoping to establish interaction maps between chemical compounds and microbes, individually and in communities using advanced multi-omics approaches, with application for human (e.g., individualised diet) or planetary health (e.g., pesticide response biomarkers).<\/p>\n\n\n\n

And this latest work by Jacoby follows on a previous project he pursued \u2013 also thanks to ERI funding \u2013 that measured toxic pollutants in specific plankton species to better understand their mechanisms of bioaccumulation with the intent that his findings might also inform the design of green chemicals.<\/p>\n\n\n\n

\u201cI\u2019m quite positive about being at EMBL during this new five-year programme where I\u2019m encouraged to think about and pursue molecular approaches to planetary biology issues,\u201d Jacoby said. \u201cOur modern life has come to depend on the chemical industry for necessary pharmaceutical drugs and agricultural production. If we discontinued their use, what would happen to global health? To agricultural production? Hopefully, we can help others have information they need to build degradable replacements to these chemicals.\u201d<\/p>\n","post_title":"The power of a pesticide library","post_excerpt":"EMBL research groups apply molecular biology and its research tools to better understand agricultural pesticides\n","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"the-power-of-a-pesticide-library","to_ping":"","pinged":"","post_modified":"2023-03-31 14:36:15","post_modified_gmt":"2023-03-31 12:36:15","post_content_filtered":"","post_parent":0,"guid":"https:\/\/www.embl.org\/news\/?post_type=embletc&p=53296","menu_order":0,"post_type":"embletc","post_mime_type":"","comment_count":"0","filter":"raw"}]},"yoast_head":"\nFrom academia to industry and back | EMBL<\/title>\n<meta name=\"description\" content=\"Sara A. 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