MRC Laboratory of Molecular Biology

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'The LMB pushes the limits of knowledge and feasibility, illuminating biology with the exactness of chemistry and physics.'

The MRC Laboratory of Molecular Biology (LMB) is an internationally leading research institute dedicated to the understanding of important biological processes at the levels of atoms, molecules, cells and organisms. In doing so, we provide knowledge needed to solve key problems in human health. We seek to understand the structures of molecules and molecular machines, their fates and functions within cells, and how these make up complex systems such as cells, tissues, the immune system and the brain, often with a view on health and disease.

Founded by the Medical Research Council over 60 years ago, in the far-sighted belief that molecular biology would one day be of medical benefit, the Laboratory has indeed made revolutionary contributions to medicine – often through the development of new techniques. Advances in X-ray crystallography and electron cryo-microscopy (cryo-EM) to determine protein structures are now used for structure-based drug design, DNA sequencing is a cornerstone of molecular medicine and diagnosis, and monoclonal antibodies have become one of the most powerful therapeutic tools.

The combination of ambitious goals, a shared budget and stable long-term support has generated a unique collaborative LMB culture that values boldness and originality. It has resulted in twelve Nobel Prizes awarded for work carried out by LMB scientists, and has contributed, in part, to eleven Nobel Prizes awarded to alumni for work done elsewhere.

The LMB pushes the limits of knowledge and feasibility, illuminating biology with the exactness of chemistry and physics: computational approaches are becoming ever more powerful, biophysical methods have revolutionised molecular imaging and new approaches in chemical and synthetic biology and biotechnology provide the tools for future discoveries and applications. We also continue to promote the application of our research findings, both by collaboration with existing companies small and large and by the founding of new ones.

The LMB provides a diverse and unsurpassed environment for both young and established researchers with state-of-the-art facilities and a unique scientific culture. Our scientists are drawn from all over the world, creating a lively international community for the exchange of ideas and technical innovation. Many are inspired by the knowledge that discoveries made at the LMB have made a difference to the world, and will continue to do so.

Jan Löwe, Director

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Structural StudiesThe Structural Studies Division is working to understand the structure, function and interactions of

biologically important molecules, using techniques such as X-ray

crystallography, electron microscopy and NMR.

The Division’s focus is on long-term challenging problems that go hand-in-hand with advancing the methods used to study them. Thus, efforts to improve data analysis in crystallography and electron microscopy are accompanied by the study of major biological questions such as protein degradation, splicing and mRNA control, translation, cellular transport and signalling, and amyloid formation. Many of these areas are also important for

Protein coding genes in higher organisms are split and are first transcribed into precursor messenger RNA (pre-mRNA) consisting of coding sequences (exons) and non-coding sequences (introns). The spliceosome is the molecular machine which cuts out the introns and stitches the exons together, so that the resulting mature mRNA can be translated to produce proteins. Importantly, many human genes can undergo alternative splicing: some exons can be skipped to produce variant forms of the resulting protein. This helps regulate gene expression and increases the repertoire of proteins that can be made in different tissues and developmental stages.

The spliceosome comprises five short RNAs and approximately one hundred proteins. When Kiyoshi Nagai’s group determined the crystal structure of one of the proteins in 1990 it seemed an impossible task to obtain the atomic structure of the whole spliceosome because of its sheer size and complexity.

The group made slow but steady progress with long term funding from the MRC and finally made a major breakthrough in 2015 when they determined the first structure of a large spliceosomal assembly by electron cryo-microscopy (cryo-EM).

Subsequently they captured cryo-EM snapshots of the yeast spliceosomes in key states during assembly and catalysis which have provided crucial insights into the molecular mechanism of pre-mRNA splicing. Cryo-EM structures of the human spliceosome begin to reveal new tissue or gene-specific regulatory events in humans, which help us understand the pathology of some genetic diseases.

understanding and developing cures for various diseases.

Research groups within the Division are also dedicated to developing computational methods for the analysis, interpretation and use of the wealth of data rapidly accruing from the structures of molecules as well as from sequencing of whole genomes. This work is likely to lead to a better understanding of the large-scale networks that are involved in the regulation of genes and the interactions of proteins in the cell.

Science in the LMB is organised in four research Divisions with their own strengths and goals. While the science covers a broad range, the common theme is the emphasis on understanding biological processes at the molecular level. Fundamental studies that offer opportunities for medical applications or technical innovation are supported and encouraged.

Kiyoshi comments: 'Long-term support from the MRC has been crucial in tackling fundamental problems, that seemed impossible to solve when we started working on them. Our work has benefited enormously from equally long-term efforts to develop cryo-EM techniques by Richard Henderson, Sjors Scheres and their colleagues. The collegial atmosphere of the LMB allows us to interact and help each other at all levels’.

'In a factory you know what you're going to make. Here, we plant things that grow and mature. It takes a long time.' Aaron Klug

Difficult problems - Long-term view

Left: The yeast spliceosome immediately after completing the exon joining reaction which removes non-coding genetic information. Mature mRNA with a continuous protein coding sequence is subsequently released from the spliceosome

Research Research

Left to right: Structure of the HIV-1 capsid core determined inside the virus by electron cryo-tomography | The microtubule motor dynein (grey) bound to dynactin (multicolour) via the cargo adaptor BICD2 (orange). Image by J Iwasa | Cryo-EM structure of the polymerase module of the cellular machinery (CPF) that processes mRNA 3'-ends in eukaryotes

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Basic biology - Better health

PNACResearch groups within the Protein and Nucleic Acid Chemistry (PNAC) Division are working to gain insights into human biology

and disease to help develop strategies for diagnosis and treatment. The Division’s research focuses on the biological processes leading to immunity and cancer, employing diverse approaches that range from molecular, cellular and transgenesis to genomics, proteomics and molecular evolution.

Fundamental questions such as how the molecules of life evolved on Earth are approached using organic chemistry and in vitro engineering of synthetic biological polymers. The aim is to discover the chemical origins of RNA and DNA and of the primitive genetic code, but also to evolve novel types of nucleic acids in the test tube and to create a parallel synthetic protein translation system in prokaryotic cells. These new tools will be applied to fundamental biological research

and ultimately could lead to novel molecular scaffolds for therapeutic applications.

Research groups in the Division are also studying the inter- and intra-cellular pathways that protect organisms from infection as well as those that maintain tissue homeostasis and which are often aberrantly activated in cancer. Efforts are directed to uncover the mutational processes that underpin genomic changes in cancer and the molecular mechanisms preserving the genomes of stem and proliferating cells from such damage. A common goal is to identify and understand the key molecules which guard against infection and cancer to help develop new strategies for rational, molecule-led therapeutic approaches.

The Centre for Chemical and Synthetic Biology (CCSB) combines molecular and cellular biologists working closely with innovative organic chemists to apply chemical biology and molecular engineering of biological systems to solve fundamental questions in biology.

Andrew McKenzie's research looks at how immune cells coordinate the body defence against pathogens, in particular the role of soluble molecules, known as interleukins, such as IL-25. This work is providing crucial insights into many diseases where the normal regulation of the immune system goes awry, such as autoimmunity and asthma.

Asthma is a common chronic disorder characterised by inflammation and hyperreactivity of the airways, which afflicts around 300 million people worldwide. The disease symptoms are complex and variable in severity and the causes are still poorly understood. Although the majority of asthma sufferers respond to medication with steroids, such treatment can be associated with a number of side-effects and a proportion of sufferers (5 – 20%) develop a form of severe asthma that is not controlled by standard treatments.

The discovery of a new immune cell, that is induced by IL-25, has dramatically changed the understanding of allergic diseases and more fundamentally of how immune responses get started, but has also led the McKenzie group to develop inhibitory monoclonal antibodies to human IL-25, which have been shown to prevent many of the symptoms of asthma in models of human disease.

These antibodies have been 'humanised’ using a method pioneered at the LMB and are undergoing further development to evaluate their therapeutic potential.

As Andrew explains: ‘By studying the cytokine, IL-13, which induces mucus secretion and contraction in the airways, we discovered a previously unappreciated immune cell type called innate lymphocytes (ILC2). ILC2 cells respond to the cytokines IL-25 and IL-33 by proliferating and producing high levels of IL-13, orchestrating the initiation of allergic asthma.’

Above: Influx of T cells (red) and IL-13-producing ILC2 cells (green) in the lung

Research Research

'Discoveries in basic science lead often, in unpredictable ways, to medical advancements.' César Milstein

Left to right: Activation of human VPS34 complex II by Rab5-associated lipid membranes | Super-resolution image of Salmonella bacteria in the cytosol of a human cell detected by Galectin-8 (green) and NDP52 (blue)

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Young scientists - Innovative research

Cell BiologyThe cell is the fundamental unit of life. Some organisms, such as a bacterium or yeast, are composed of a single cell

whereas many trillions of cells make up a human. The

cells in our body are organised into various tissues where they perform specialised functions important for normal health. The Cell Biology Division aims to understand the inner workings of individual cells, how cells become specialised and organised into tissues, and how defects in cellular function or organisation contribute to human disease.

Research groups within the Division employ a range of methods. Tissues, cells, and even individual molecules are directly visualised and tracked using cutting-edge light and electron microscopy. Genetic methods, genome

editing, and protein biochemistry are used to dissect and manipulate cellular processes at a molecular level. Collectively, these methods provide understanding of the precise mechanisms underlying complex physiology and pathology.

Studies of how the inside of a cell is organised and built typically use cells in culture, yeast, and protein biochemistry. This research is revealing how new proteins are made and trafficked to the correct location inside cells, how molecular motors move cargo around the cell, and how organelles inside the cell are positioned and communicate with each other.

Studies of tissue formation, organisation, and function make use of nematodes, flies, mice, and organ cultures. This work shows how collections of cells migrate and interact to form organs, how neurons assemble into functional networks, and how cell and tissue function is regulated by the time of day.

Left to right: Epidermis of a Drosophila embryo, with cell-cell junctions labelled in red and blue, and an actin-binding protein labelled in green | Snapshot of reconstituted mRNA-motor complexes (magenta) translocating along microtubules (green) bound to a glass surface | Section through a bud of an early embryonic mouse lung. Cell-cell junctions are labelled in red, nuclei in blue

The human brain is a big and powerful information-processing machine. The architecture of the cells within is critical to its function, but is inaccessible to researchers. In particular it is difficult to understand how it becomes organised as it grows in the embryo.

Madeline Lancaster is looking at how human brains are built under the microscope. She has developed a model system, called cerebral organoids, or mini-brains for short, that allow her to follow human brain development in a petri dish. Through a process of directed differentiation in a supportive 3D microenvironment, tissues generated from human pluripotent stem cells can spontaneously self-organise to form the stereotypic organisation of the embryonic brain, allowing her to explore how neural precursor tissues develop into the complex structures of the human brain. Above: An image of a cerebral organoid with neurons

labelled with a fluorescent protein. Axons, or nerve fibres, have extensively grown out over many hours of imaging

Cerebral organoids can model neurodevelopmental disorders, such as microcephaly, a disorder characterised by a significantly reduced brain size, and potentially can be used to understand the molecular basis of other neurodevelopmental disorders like autism and intellectual disability.

In Madeline's words: 'My lab is interested in one of the greatest puzzles in human history: how the human brain is unique. To begin addressing this, we use 3D developing human brain tissue in a dish and examine its many unique characteristics. Our hope is that a greater understanding of human brain development will lead to better treatments for a variety of neurological conditions.'

Research Research

'Innovation is driven by the curiosity to answer fundamental questions.' Michael Neuberger

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Human disease - New molecular insight

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases, affecting over 40 million people worldwide. A shared characteristic is the presence of filamentous amyloid assemblies within brain cells. Similar inclusions are also found in related disorders, including Pick’s disease, chronic traumatic encephalopathy, progressive supranuclear palsy, dementia with Lewy bodies and multiple system atrophy. Existing therapies deal, at best, with the symptoms of these diseases.

Work carried out by Michel Goedert and collaborators has helped to identify tau protein and alpha-synuclein as the major components of the pathological filaments and to show that their formation causes cell death and neurodegeneration. Recent work done in collaboration with the group of Sjors Scheres has used electron cryo-microscopy (cryo-EM) and immunogold negative-stain electron microscopy to determine the first high-resolution structures of disease filaments from human brain, thus identifying different conformers of assembled tau in Alzheimer’s and Pick’s diseases.

NeurobiologyOne of the biggest challenges facing the biological sciences is to

understand how brains can give rise to minds. The

nervous system is a complex machine, but at its simplest it consists of nerve cells (neurons), their connections (synapses) and the circuits they thereby create. The Neurobiology Division aims to understand the fundamental properties of neurons, synapses, and circuits and how they behave both in health and disease. This will increase understanding of how networks of cells give rise to thoughts and control behaviour. What is the molecular basis of synaptic function, how is information processed through circuits and what molecular mechanisms underlie common neurodegenerative diseases?

A broad combination of biochemistry, structural biology, imaging and electrophysiology is used to build up a detailed picture of how synaptic vesicles release neurotransmitters, how ion channels are trafficked to the cell surface and, once there, how neurotransmitters released by synaptic vesicles trigger opening of the channels.

Analysis of sensory transduction and the processing of olfactory information in the brain, as well as the organisation and function of neuronal networks controlling movement and circadian rhythms, such as sleep is revealing how the properties of nerve cells determine the

flow of information within circuits and how this translates into behaviour.

Researchers in the Division are also unravelling the molecular and cellular mechanisms by which cells adapt protein synthesis in response to stress, and how the abnormal assembly of a small number of proteins causes common human neurodegenerative diseases. By defining general mechanisms of protein quality control and aggregation, the aim is to identify novel therapeutic approaches to manage conditions such as Alzheimer’s and Parkinson’s diseases.

Top to bottom: Image from the brain of an experimental mouse with neurons and their processes containing filamentous aggregates of human tau (in brown) | Schematic of the Alzheimer and Pick folds, based on cryo-EM analysis. These structural insights will inform understanding of how diseases start and how they may be treated

Top to bottom: The molecule that mediates inhibition in the brain. Cryo-EM high resolution structure of the GABA-A receptor informs our understanding of its function in epilepsy, anxiety, and addiction | Observing living neurons in the transparent worm, C. elegans. Genetically encoded red and green fluorescent markers show where particular neurons are located and when they areactive

Research Research

'We're not asked to find cures for diseases, but to provide the background that allows disease processes to be better understood.' John Walker

Alzheimer Fold

Pick Fold

Michel comments: 'Our work is aimed at understanding the mechanisms by which the normally soluble tau and alpha-synuclein proteins assemble into abnormal filaments. In due course, this work may lead to the development of mechanism-based therapies for tauopathies and synucleinopathies.'

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Environment

The LMB is at the heart of the expanding Cambridge Biomedical Campus, one of the largest and most internationally competitive concentrations of healthcare-related talent and enterprise in Europe. The campus is on the south side of the city, with easy connections by rail and road, and in walking or cycling distance to the University, the countryside and residential areas.

The distinctive LMB building – in the shape of a chromosome, with two laboratory blocks joined by a central atrium, was designed to provide maximum flexibility for the future, including space for specialist new equipment and new facilities as they are developed.

The laboratory is easy to navigate; its open airy walkways, spacious rooftop restaurant, fully equipped lecture theatre and library, and comfortable coffee and breakout rooms on each floor all facilitate the LMB’s distinctive

'There have been very good research institutions that have triedto capture the flavour and spirit but they haven't got it.'

Joan Steitz, discoverer of snRNPs, on the LMB

*http://www.med.cam.ac.uk/university-research-unit/

culture – encouraging close interaction within groups, and an open, collaborative and dynamic way of working.

This culture is mirrored by the Cambridge Biomedical Campus – by mixing together basic academic science, hospital practitioners and clinical research together with international industrial enterprises, the Campus offers a unique environment to enable the exchange of ideas and technical innovation.

Scientists from the University of Cambridge Clinical School* are already working alongside LMB scientists, and collaborative links with academics at the CRUK Cambridge Institute, Cambridge Institute of Medical Research, and the Wellcome Sanger Institute as well as with industrial partners such as AstraZeneca and MedImmune thrive, aided by the geographical proximity and shared interests.

Environment

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New challenges -Technological advances

The LMB is noted for its development of new techniques and technologies to help advance research. LMB’s researchers have easy access to some of the world’s highest quality scientific technologies on site and the right environment to foster innovation.

Since the mid 1980s, the LMB along with other institutions has helped to pioneer electron cryo-microscopy (cryo-EM) techniques to help study the three-dimensional structure of macromolecules both as two-dimensional crystalline arrays as well as single particles without the need to crystallise the samples first. Following a procedure invented by Jacques Dubochet’s group at EMBL in the 1980’s, a solution of the chosen biomolecule is frozen in a thin layer of ice, and this layer is imaged in an electron microscope. Many thousands of images, from different orientations, are needed to determine the structure of each biomolecule. These are then computationally assembled into a three-dimensional image to give the structure of the macromolecule.

Richard Henderson’s identification of key bottlenecks in the process led to the development of a new type of direct-electron detector – with impetus from him and Wasi Faruqi. Work by Sjors Scheres' group at the LMB has combined data from such detectors with new methods of image processing, resulting in structures of greatly increased resolution.

Sjors comments: 'The recording of movies by these new cameras allows tracking of the movement of individual complexes while the sample is exposed to the electron beam. As a result, structures to near-atomic resolution from cryo-EM images can be obtained.'

Above: Average cryo-EM images of 80S ribosome particles

Environment

A cornerstone of LMB science is the provision of excellent facilities and support services – freely available to all members of the Laboratory, from PhD students to group leaders. These are led and staffed by experienced scientists with the expertise to carry out large-scale projects and to aid collaborative research across the LMB’s Divisions.

Biological Mass Spectrometry & Proteomics Mass spectrometry has changed the way systems-

level analysis of biological samples is undertaken. Headed by Mark Skehel, the facility aims to cover all aspects of protein mass spectrometry, with a particular focus on structural proteomics. The facility is equipped with a comprehensive range of instrumentation including a Thermo Scientific Q Exactive HF-X and a Waters SYNAPT G2 Si HDMS.

Electron Microscopy The facility, managed by Shaoxia Chen, has ten electron microscopes, which provide flexible options for 2D

and 3D structural analysis of biological material by cryo-EM. These consist of five state-of-the art 300 keV FEG cryo-transmission electron microscopes (three Titan Krios and two Polaras), as well as five other electron microscopes, including a Scios DualBeam scanning electron microscope.

Light Microscopy Headed by Nick Barry, an optical physicist and specialist in light microscopy, it houses four new super-

resolution microscopes and supports specialist advanced microscopy throughout the building.

Crystallisation and X-ray Infrastructure for

crystallography includes automated systems for formulating and setting up

crystallisation trials, under the expert assistance of Fabrice Gorrec. The usefulness of the crystals obtained is determined with in-house X-ray diffractometers. To solve structures, LMB scientists can proceed with remote data collection after shipping crystals to the Diamond synchrotron in Harwell or the European Synchrotron Radiation Facility in Grenoble.

Facilities

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Biophysics The facility, overseen by Chris Johnson and Stephen McLaughlin, has a wide range of instruments to

investigate the affinity and dynamics of molecular processes at a multi-scale level, from ensembles in solution down to single molecules. State-of-the-art instruments, such as the SwitchSENSE, support cutting-edge research.

Flow Cytometry The facility operates jointly with the University of Cambridge School of Clinical Medicine and is run by Maria

Daly. It enables researchers to characterise, quantify and separate cell populations on the basis of surface and intracellular markers. It includes high-speed cell sorters, several multifluorescent analysers and a spectral analyser.

Biological Services A group of more than 70 animal technicians maintain the facilities to house breeding and experimental

colonies of rodents. They provide the highest standard of modern transgenic production services and experimental resources, with a strong emphasis on animal welfare and the 3Rs, to support the scientific programmes of the LMB and some MRC University Units in Cambridge.

Nuclear Magnetic Resonance The solution-state NMR facility houses 500, 600, 700 and 800 MHz Bruker systems

in a dedicated building. LMB groups have instant access to wide-ranging expertise in all aspects of biomolecular NMR methods. This includes help with protein expression, data acquisition and often the complete data analysis in a collaborative effort, under the direction of Stefan Freund.

Scientific Computing Computational resources at the LMB include GPU and large memory servers, together with a 3912 CPU

High Performance Computing (HPC) cluster, and additional data storage of up to 4.6PB. An expert team, headed by Jake Grimmett, provides advice on computational problems.

Workshops The LMB’s scientists also benefit from access to state-of-the-art workshops, headed by Andy Howe and Steve

Scotcher. In practical terms, having Electronics and Technical Instrumentation Workshops on site means that design, prototyping and development happen far faster at the LMB than in most other laboratories, which rely on outside contractors.

Facilities

Many of the outstanding questions in biology and medicine are difficult to address because there is no way to directly look at the complex molecular machines responsible for life.

Christopher Russo works on developing new instruments and methods for imaging biological molecules (DNA, RNA and proteins) at atomic resolution using electron microscopes. This requires improved cryo-preparation and imaging methods that can be applicable to any biological specimen. Christopher is studying the physical principles underlying the current resolution limits and reengineering the critical components in the imaging system to improve resolving power using recent advances in nanoscience, solid-state physics, surface chemistry, electrical engineering and materials science.

Christopher says: ‘The LMB houses state-of-the-art technical instrumentation and electronics workshops that allow us to design and build our own scientific instruments and push forward what is possible. This is essential to our work on improving electron microscopy and to the advancement of biology generally.’

'Progress in science depends on new techniques, new discoveries and new ideas, probably in that order.'

Sydney Brenner

Engineering - At the edge of biology

Right: 3D representation of an ultrastable, all gold specimen support developed and made at the LMB.

Scale bar is 10 micrometers

Facilities

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Supporting scientists and sustaining a robust and flourishing environment for world-class research will be a key element in the LMB’s continuing success.

STAFF (approximate numbers)

Group leaders

Postdoctoral/support scientists

PhDstudents Support staff Scientists in the University of Cambridge

Molecular Immunity Unit

50 400 100 200 70

John Briggs completed his DPhil in structural biology at the University of Oxford, before working as a postdoctoral research fellow at Ludwig Maximillians University Munich and then starting his own group at

the European Molecular Biology Laboratory in Heidelberg. John received the Royal Microscopical Society Medal for Life Sciences in 2015, was a Finalist in the 2018 Blavatnik Awards for Young Scientists in the United Kingdom and is a member of EMBO.

John’s group is studying the structures of cellular trafficking vesicles and of enveloped viruses such as HIV-1 and influenza A virus. Viruses and vesicles are extraordinary self-assembling machines, and John and his group are aiming to uncover the mechanisms that underlie their assembly and disassembly. To do this, they have developed methods for electron cryo-tomography as well as for cryo-correlative fluorescence and electron microscopy.

As John explains: 'Our research has really benefited from collaborations in the past and there is enormous potential for developing new collaborations within the LMB. We are already learning a lot from our new LMB colleagues and they are excited to use the methods we are developing in their own research.'

Radu Aricescu joined the LMB in 2017, having been an MRC Senior Research Fellow and Professor of Molecular Neuroscience at the University of Oxford. His group is interested in understanding the

molecular mechanisms responsible for acquisition and storage of information in the brain. Previously, Radu had received undergraduate training at the University of Bucharest, before completing a PhD in developmental neurobiology at University College London and then spending time as a post-doctoral researcher in structural biology at the University of Oxford.

Radu’s group is using a combination of structural biology methods, including X-ray crystallography, electron cryo-microscopy and electron cryo-tomography, to solve structures of the key neurotransmitter receptors at excitatory and inhibitory synapses. This will provide fundamental mechanistic insights into the basic biology of neurotransmission and increase understanding of the synaptic dysfunction associated with ageing and disease.

As Radu explains: 'Our research is tackling big questions about synaptic function, and the LMB is the ideal place where one can pursue such long-term goals. The electron cryo-microscopy facilities and expertise at the LMB are world-class, and will be of huge value to my group in our quest to ultimately determine the molecular mechanisms of neurotransmission in a physiological context.'

Attracting scientists - UK and worldwide

People

More than 800 scientists and support staff work in the LMB, with around 550 directly carrying out research in more than 50 groups.

The LMB attracts some of the best people from around the world – at all stages of their careers. Over 50 nationalities are represented, with more than half of the group leaders originating from outside the UK – a truly international community of PhD students, postdoctoral scientists and researchers.

The LMB’s intellectual base and unique culture – developed over the last 70 years – remains important in attracting and retaining key scientists. Many groups in the Laboratory are small, consisting of eight or fewer people under the leadership of a senior researcher. These small groups help to maintain the dynamism and flexibility of research at the LMB, and encourage close interactions both within groups and throughout the Laboratory.

This interaction is further fostered by an open intellectual environment, a wealth of freely-shared services and resources, and generous central funding.

Although it can claim to be the birthplace of modern molecular biology, the LMB is now one of many laboratories carrying out outstanding research and competing to recruit the world’s best scientists. The LMB’s state of-the-art laboratory space, equipment and facilities help the Laboratory to compete for new talent.

In addition to dedicated administrative help, all staff at the LMB have access to a wide range of support services including high quality IT support, an expert Library and Information Service, experienced creative help from the Visual Aids team and practical support from stores and purchasing. The aim is to free scientists from distractions and enhance their ability to disseminate their science.

People

Origin and destination of research students working at the LMB 2009 – 2015.

COUNTRY OF ORIGIN

UK 30.2%

Australia 2.0%Africa 0.4%

Asia 11.8%

South America 3.7%

North America 5.7%

Europe (non EU) 6.1%EU 40.0%

TOTAL245

Other 11%

USA 19%

EU 16%

UK 53%DESTINATION TOTAL

146

Not employed immediatelyafter leaving lab 3%

Non-science7.5%

Medicine/further training

5.5%

Science related 10%

Academic postdoc 74%

NEXT CAREER TOTAL146

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Building an international science community

'The LMB provides a wonderful environment for students...although attached to a research group, the whole lab is, in essence, their playground meaning they can - and often do, approach anyone in the building who can help with their project.'

Cristina Rada, LMB Director of Graduate Studies

Scientific alumni: known locations [December 2015]

Destination of postdoctoral fellows trained at the LMB from 2009- 2014.(258 total)

UK 93 Research (85%) Science related (6%) Other (6%) Unknown (2%)

Europe 81 Research (90%) Science related (9%) Other (1%) Unknown (0%)

Rest of world 84 Research (70%) Science related (7%) Other (0%) Unknown (23%)

'Scientific research is one of the most exciting and rewarding of occupations. It is like a voyage of discovery into unknown lands, seeking not for new territory but for new knowledge.' Fred Sanger

Educating the next generation

Training scientific talent

People People

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Shaping science across wide horizons The LMB International PhD programme attracts students of outstanding potential for research from the UK and all over the world, and then provides them the freedom, guidance and resources to pursue cutting-edge projects from the day they arrive.

Students are at the heart of, and in many cases lead, some of the most important science emerging from the LMB. Although attached to individual groups, they are encouraged to seek any relevant expertise or resource in the building that helps their research. The small group sizes, the communal nature of the resources within the Lab and the dedicated staff who run lab facilities all conspire to enlarge the scope and ambition of the projects undertaken by the students and more importantly facilitate their successful completion.

Encouragement to promptly complete their PhD thesis, coupled with support for short post-doctoral extensions to finalise and publish work, enables LMB students to make their mark and fully develop their potential. LMB students produce on average 3.4 publications over their time in the Lab, with more than half of those as

first authors. After completing their PhD, 74% of LMB students move to postdoctoral positions in academia, and many start their own research groups within 5-10 years – our most recent survey shows 29% of female and 26% of male students have done so.

The LMB supports the wider scientific community by supplying highly trained leaders in academic research. They leave the LMB to develop and support molecular science in the UK and around the world. Between 2005-2010, 85% of the postdocs trained at the LMB continued onto research careers, 41% of the females and 60% of the males became group leaders by 2015.

Tanmay Bharat (2013-2017) Tanmay started his own group at the Sir William Dunn School of Pathology, University of Oxford in 2017. He was a post-doctoral fellow with Jan Löwe at the LMB

and had previously trained as a graduate student with John Briggs at the EMBL in Heidelberg. Whilst at the LMB, Tanmay solved the structure of the bacterial actin homologue ParM to reveal how it drives plasmid DNA segregation in growing bacteria.Bharat, T.A., Murshudov, G.N., Sachse, C., Löwe, J. (2015) Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles. Nature 523, 106-110. | Bharat, T.A., Russo, C.J., Löwe, J., Passmore, L.A., Scheres, S.H. (2015) Advances in single-particle electron cryomicroscopy structure determination applied to sub-tomogram averaging. Structure 23, 1743-1753.

Susan (Sichen) Shao (2012-2016) Susan started her lab at the Cell Biology department at Harvard Medical School as an Assistant Professor in 2016. She was a PhD student with Manu Hegde and

moved with him to the LMB. During her subsequent postdoc, she performed the reconstitution and functional analysis of the ribosome-associated ubiquitination pathway and solved its structure. She has since applied her methods to investigate the process of stop codon decoding, and in collaboration with the Ramakrishnan lab she has determined the structure of the ribosome in combination with mammalian release factor.

Shao S., von der Malsburg K., Hegde R.S. (2013) Listerin-dependent nascent protein ubiquitination relies on ribosome subunit dissociation. Molecular Cell 50(5):637-648. | Shao S., Hegde R.S. (2014) Reconstitution of a minimal ribosome-associated ubiquitination pathway with purified factors. Molecular Cell 55(6):880-890.Brown A., Shao S., Murray J., Hegde R.S., Ramakrishnan V. (2015) Structural basis for stop codon recognition in eukaryotes. Nature 524(7566):493-496. | Shao S., Brown A., Santhanam B., Hegde R.S. (2015) Structure and assembly pathway of the ribosome quality control complex. Molecular Cell 57(3):433-444.

Melina Schuh (2009-2016) Melina was appointed Director at the Max Planck Institute in Göttingen in 2016. After completing her PhD in 2008 at the EMBL in Heidelberg, Melina started her own research

group at the LMB in 2009 looking at how diploid oocytes mature into haploid eggs. Her work explained some of the causes of aneuploidy – a defect in the assortment of the chromosomes in the egg and a common cause of infertility – and developed methods to systematically analyse defects linked to abnormal chromosome segregation during meiosis.Schuh M. (2011) An actin-dependent mechanism for long-range vesicle transport. Nature Cell Biology 13(12):1431-1436. | Holubcová Z., Howard G., Schuh M. (2013) Vesicles modulate an actin network for asymmetric spindle positioning. Nature Cell Biology 15(8):937-947. | Pfender S., Kuznetsov V., Pasternak M., Tischer T., Santhanam B., Schuh M. (2015) Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes. Nature 524(7564):239-242.

Training Training

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In 2007 the LMB’s Richard Henderson and Chris Tate co-founded Heptares Therapeutics to exploit pioneering new technology to stabilise G-protein-coupled receptors (GPCRs). Heptares is now wholly owned by Sosei.

Because they play a crucial role in many diseases, GPCRs are the targets of 25-30% of all modern drugs.

As Chris comments: 'GPCRs are an important family of proteins found in cell membranes, which are responsible for triggering responses inside cells to external factors such as hormones, neurotransmitters and sensory stimuli. Commonly prescribed drugs, such as beta-blockers and anti-migraine drugs, specifically interact with these receptors. Understanding the structure of GPCRs at a molecular level is important in designing new and more effective drugs to combat many human illnesses.

Heptares’ StaR (Stabilised Receptor) technology platform allows us to apply contemporary drug discovery approaches to stabilised GPCRs – improving the chances of finding drugs to previously intractable targets and enabling the development of safer and more selective therapeutic agents.'

Heptares is using this technology to work on its own and with partners to discover new medicines to target key diseases such as Alzheimer’s, schizophrenia, type 2 diabetes, cancers and HIV. In 2015, Heptares was bought for 400 million USD by the Sosei Group, a leading Japanese biopharmaceutical company. Four drug candidates have recently entered clinical trials for cognitive decline, psychosis and cancer.

Structure of the adenosine A2A receptor. Top to bottom: View of the receptor in the membrane showing how the agonist adenosine binds (inset) | Structure of the receptor bound to a preclinical candidate developed by Heptares Therapeutics for the treatment of Parkinson’s disease. [PDB codes 2YDO and 3UZC, respectively].

The LMB has an enviable track record in promoting the application of its research findings. Researchers at the LMB benefit from the Laboratory’s long experience in this field, and from being able to access expert advice on how best to exploit their discoveries – whether by the licensing of patents, collaborations with existing companies or by founding new spin-off companies.

The LMB has also benefited by generating significant sums to invest in future scientific research, generating over £700 million in commercial income.

Inevitably, the Laboratory’s focus on curiosity-driven and long-term basic research means that there is often a long ‘development gap’ between discovery and bringing a drug to market. Progress may take time but there have been spectacular successes, including the development of humanised monoclonal and synthetic antibodies – which now make up a third of all new drug treatments for a variety of diseases, including cancer, arthritis and asthma.

When intelligently exploited, this type of research pays handsome dividends for both human health and UK industry. For example, the licensing of the LMB’s work on human antibodies to local start-up company Cambridge Antibody Technology led to the development of Humira®, a key drug in the treatment of rheumatoid arthritis. The development of

this and other therapeutic antibodies earned the LMB's Greg Winter the Nobel Prize for Chemistry in 2018.

Other notable contributions include the development of laser-scanning confocal microscopes and the spin-off, Heptares Therapeutics, exploiting structural analysis of G-protein-coupled receptors for drug design.

Scientists at the LMB are engaging with industry to bring promising new methods and discoveries towards practical application. The location of AstraZeneca adjacent to the Laboratory has led to a joint collaboration fund to foster interactions, and other biomedical companies including Pfizer, GlaxoSmithKline, Heptares and Eli Lilly also fund work at the LMB. Methods to determine atomic structures of macromolecules by electron microscopy, developed at the LMB, are being transferred to industry to further its own research and development.

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1947: MRC ‘Unit for Research on the Molecular Structure of Biological Systems’ established

1953: Double-helical structure of DNA elucidated

1953: Sliding filament model for muscle contraction proposed

1959: First atomic resolution map of a protein, myoglobin 1959: Structure of

haemoglobin determined

1961: Demonstration of the triplet nature of the genetic code

1962: MRC Laboratory of Molecular Biology opened 1967: First mutant of C. elegans

(nematode worm) produced

1968: First 3D models of protein structures from electron microscopy

1971: Precursor tRNA molecules found and discovery of catalytic RNA

1972: Asymmetric lipid bilayer structure for biological membranes proposed1972: Signal peptide

sequence which directs protein secretion discovered

1975: Monoclonal antibody methodology invented

1975: First 3D structure of a membrane protein, bacteriorhodopsin

1977: Method for sequencing DNA developed

1983: Embryonic cell lineage of C. elegans unraveled

1986: First humanised antibody produced

1986: C. elegans is the first animal to have its entire nervous system mapped

1988: First patient treated with humanised antibody, Campath-1

1989: First LMB spin-out company, Cambridge Antibody Technology, formed

1994: Structure of F1 subunit of mitochondrial ATPase revealed

1997: Major component of filamentous lesions found in Parkinson’s disease identified 1998: C. elegans is the first

animal to have its genome sequenced

2000: Structure of 30S ribosomal subunit and its complexes determined

2008: β-adrenergic receptor structure determined

2014: Cryo-EM atomic structures at 3.2Å resolution

2013: New MRC Laboratory of Molecular Biology building opens

2002: Molecular mechanism of antibody mutation uncovered

2010: Discovered that antibodies fight viruses within infected cells

2015: First spliceosomal complex structures determined

2017-2018: Structures of tau filaments from Alzheimer’s and Pick’s disease solved

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Impact

Scientific Landmarks - A brief history of the LMB

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David Barford dbarford@mrc-lmb.cam.ac.uk

Molecular mechanisms of the anaphase-promoting complex and the mitotic checkpoint. We study how the anaphase-promoting complex (APC/C) recognises and ubiquitinates proteins during the cell cycle, and the basis for its regulation by the spindle assembly checkpoint.

Mariann Bienz mb2@mrc-lmb.cam.ac.uk

Molecular mechanisms of Wnt signal transduction. We study the molecular functions of individual Wnt signalling components and their mutual interactions. Ultimately, we aim at identifying and developing their potential as therapeutic targets in cancer.

Mark van Breugel vanbreug@mrc-lmb.cam ac.uk

Structure and assembly mechanisms of centrioles. We aim to understand the assembly mechanisms and molecular architecture of centrioles, essential cell organelles with key roles in cell division, sensing and movement.

Jason W. Chin chin@mrc-lmb.cam.ac.uk Systematic genetic code reprogramming / Centre for Chemical and Synthetic Biology. We are reprogramming the genetic code of living organisms via biological engineering. We are using reprogrammed codes and innovative chemistry, to provide new insight into biological processes.

Simon Bullock sbullock@mrc-lmb.cam.ac.uk

Mechanisms of mRNA localisation and cytoskeletal transport. Our goal is to shed light on how cellular components are sorted and dispersed by microtubule-based motor complexes, and how these transport processes contribute to the functions of cells within organisms.

Andrew Carter cartera@mrc-lmb.cam.ac.uk

The structure and mechanism of dynein. We use structural biology approaches and single molecule microscopy to understand how the microtubule motor dynein, the largest and most complicated of the cellular motors, transports its cargos.

Mario de Bono debono@mrc-lmb.cam.ac.uk

Genes, circuits and behaviour. We are interested in understanding how neural networks are functionally assembled, how they integrate information, and how they evolve.

Paula da Fonseca pauladf@mrc-lmb.cam.ac.uk Structure and function of cell regulatory protein complexes. The proteasome is an important target for the development of new therapeutic drugs against an increasing range of conditions. We aim at fully understanding its detailed mechanisms and regulation.

Ingo Greger ig@mrc-lmb.cam.ac.uk AMPA receptor biogenesis, structure and function.. Information transfer in the nervous system occurs at synapses, where presynaptic signals are interpreted by postsynaptic receptors. We study this process with a focus on AMPA-type glutamate receptors.

Michel Goedert mg@mrc-lmb.cam.ac.uk

Molecular mechanisms of neurodegeneration. We are unravelling the mechanisms that cause the abnormal aggregation of tau protein and alpha-synuclein and how this process results in nerve cell degeneration and human diseases.

DIVISION KEY: CELL BIOLOGY | NEUROBIOLOGY | PNAC | STRUCTURAL STUDIES

Anne Bertolotti aberto@mrc-lmb.cam.ac.uk Understanding and preventing the deposition of misfolded proteins. Our goal is to understand the mechanisms that govern the deposition of misfolding-prone proteins, why they persist in aged cells and to identify strategies that could reduce their burden in disease.

Research Groups

Gerry Crossan gcrossan@mrc-lmb.cam.ac.uk

Maintenance of genome stability in stem cells. We use a combination of mouse genetics and state-of-the-art molecular biology tools to investigate the mechanisms that prevent mutagenesis in the germline.

M. Madan Babu madanm@mrc-lmb.cam.ac.uk Regulatory genomics and systems biology. We are interested in understanding how the regulation of biological systems is achieved at distinct levels of organisation (molecules, pathways, genomes) and how these processes shape the evolution of the genome.

Radu Aricescu radu@mrc-lmb.cam.ac.uk The structural biology of synaptic connectivity. We study the architecture of neurotransmitter receptors and their supra-molecular assemblies, using purified components and in situ, aiming to understand the physiology of neuronal synapses.

John Briggs jbriggs@mrc-lmb.cam.ac.uk

Enveloped viruses and coated vesicles - electron cryo-microscopy and tomography. We are optimising and applying electron cryo-tomography methods to understand the assembly processes of enveloped viruses such as HIV-1 and influenza, as well as of membrane trafficking vesicles.

Emmanuel Derivery derivery@mrc-lmb.cam.ac.uk

Mechanisms of asymmetric trafficking. Our goal is to understand the molecular mechanisms by which the cytoskeleton controls the polarized segregation of cell fate determinants during asymmetric cell division.

Julian Gough gough@mrc-lmb.cam.ac.uk

Computational genomics. We aim to further the fields of regenerative medicine and personal genomics by using computational methods on large biological datasets, to predict factors for cell reprogramming and to predict phenotype from genotype.

Ramanujan Hegde rhegde@mrc-lmb.cam.ac.uk

Membrane protein biosynthesis and quality control. We seek to understand how secreted and membrane proteins are assembled, how cells handle mistakes in these pathways, and the diseases that arise from their failure.

Michael Hastings mha@mrc-lmb.cam.ac.uk

Molecular neurobiology of circadian timing. We aim to provide a molecular genetic explanation for the ancient conserved process of circadian timing; to understand how the central and peripheral biological clocks together co-ordinate our metabolic and physiological rhythms.

Richard Henderson rh15@mrc-lmb.cam.ac.uk

High resolution 3D structures by electron cryo-microscopy. We aim to determine the atomic structure of interesting or important membrane proteins and membrane protein complexes using cryo-EM.

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Jan Löwe jyl@mrc-lmb.cam.ac.uk

The bacterial cytoskeleton. We investigate biological systems involving prokaryotic filamentous proteins that are involved in mechanical processes such as constriction and DNA segregation during cell division.

Liz Miller emiller@mrc-lmb.cam.ac.uk

Protein transport and quality control in the secretory pathway. Our work is aimed at understanding basic mechanisms of secretory protein biogenesis, focusing on protein quality control within the ER.

Kiyoshi Nagai kn@mrc-lmb.cam.ac.uk Crystallographic and functional studies of the spliceosome. Our aim is to understand the molecular mechanism of pre-mRNA splicing and provide insights into the evolutionary origin of the spliceosome.

Garib Murshudov garib@mrc-lmb.cam.ac.uk

Computational crystallography. We develop computational, statistical and structural bioinformatic tools for the analysis of macromolecular crystal structures, in particular dealing with limited and noisy data.

David Neuhaus dn@mrc-lmb.cam.ac.uk

Solution structure by NMR spectroscopy. We study the structure and the interactions of biological macromolecules and their complexes in solution employing modern NMR and isotope labelling techniques.

Andrew McKenzie anm@mrc-lmb.cam.ac.uk

Transgenic models of immune and haematopoietic disorders. We focus on understanding the molecular regulation of the immune responses underlying allergy and asthma, with the aim of identifying novel pathways for therapeutic intervention.

Sean Munro sean@mrc-lmb.cam.ac.uk

The organisation of membrane traffic by G proteins. We investigate how each organelle acquires a unique set of active G proteins, and how these then control the structure of organelles and direct the traffic between them.

Madeline Lancaster mlancast@mrc-lmb.cam.ac.uk

Human brain development in cerebral organoids. We are studying cellular mechanisms underlying human brain development to understand neurodevelopmental disease progression and to identify potential therapeutic avenues.

Harvey McMahon hmm@mrc-lmb.cam.ac.uk

Membrane curvature as an organising principle for eukaryotic cell biology. Our work is elucidating the mechanisms of membrane bending, their role in membrane fission and fusion to understand and identify known and novel pathways of receptor trafficking.

Gregory Jefferis jefferis@mrc-lmb.cam.ac.uk Olfactory perception in the fruit fly. We use a combination of genetic labelling and manipulation, targeted in vivo whole cell patch clamp recording and high resolution computational neuroanatomy to understand how smell turns into behaviour in the fruit fly.

Wanda Kukulski kukulski@mrc-lmb.cam.ac.uk

Linking membrane architecture to function by correlative microscopy. We study how membrane dynamics controls cargo traffic through the network of endosomes, and the role of membrane architecture at contact sites between organelles.

Patrycja Kozik pkozik@mrc-lmb.cam.ac.uk

Dendritic cells and initiation of the immune responses. Our goal is to build a detailed picture of the molecular events involved in antigen cross-presentation by dendritic cells, and to understand how antigen processing is regulated in viral infection and cancer.

Philipp Holliger ph1@mrc-lmb.cam.ac.uk

Synthetic biology of nucleic acid replication. We are developing in vitro systems for directed evolution to create novel, DNA-like polymers, for applications in nanotechnology and material science.

Leo James lcj@mrc-lmb.cam.ac.uk

Intracellular Immunity. Viral and bacterial pathogens evading the immune system are still able to infect cells. We are investigating how cells defend themselves against infection by intracellular pathogens.

Venki Ramakrishnan ramak@mrc-lmb.cam.ac.uk

Structure of the translational apparatus. We are currently interested in translation initiation in both bacteria and eukaryotes, as well as how certain viral sequences disrupt the process in eukaryotes.

KJ Patel kjp@mrc-lmb.cam.ac.uk Chromosome breakage and repair in stem cells. We study the origins and identity of genotoxic metabolites, the nature of the DNA damage they cause and how cells, in particular stem cells, remove and repair it.

Hugh Pelham hp@mrc-lmb.cam.ac.uk

Membrane protein sorting. We study how proteins are sorted within cells and in particular how, if they are damaged or unwanted, they are marked by ubiquitination for subsequent destruction.

John O'Neill oneillj@mrc-lmb.cam.ac.uk

Cellular rhythms, signalling and metabolic regulation. We explore the biochemical basis of circadian timekeeping and how biological rhythms integrate with other cellular systems to orchestrate temporal control of metabolism.

Lori Passmore passmore@mrc-lmb.cam.ac.uk

Molecular machines that regulate mRNA polyA tails. Our aim is to establish fundamental principles underlying the assembly of multi-protein complexes, like the Cleavage and Polyadenylation Factor (CPF) in order to understand their cellular function.

DIVISION KEY: CELL BIOLOGY | NEUROBIOLOGY | PNAC | STRUCTURAL STUDIES

Felix Randow randow@mrc-lmb.cam.ac.uk

Cell-autonomous and innate immunity. Guided by the importance of cell-autonomous immunity as the sole defender of unicellular organisms, we investigate how mammalian cells sense invading pathogens and protect their interior against them.

Research Groups

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Chris Tate cgt@mrc-lmb.cam.ac.uk

Structural biology of integral membrane proteins. We are determining the structuresof medically-relevant membrane receptors and transporters to understand their mechanism of action and for facilitating drug development.

Marco Tripodi mtripodi@mrc-lmb.cam.ac.uk

Neural circuits for perception to motor integration. We study the neural circuits responsible for the emergence of motor behaviour, focusing on the genetics of their assembly and their function during voluntary and automatic movements.

Roger Williams rlw@mrc-lmb.cam.ac.uk

Structural studies of phospholipid signalling. We are trying to develop a detailed structural understanding of the network of interacting pathways involved in phospholipid signalling, including the structures of endosomal and autophagosomal protein complexes.

John Sutherland johns@mrc-lmb.cam.ac.uk

Chemical origins of molecular biology. We are interested in uncovering prebiotically plausible syntheses of the informational, catalytic and compartment–forming molecules necessary for the emergence of life.

Joe Yeeles jyeeles@mrc-lmb.cam.ac.uk

Mechanisms of chromosome replication. We aim to understand how the chromosome replication machinery copies vast amounts of DNA while minimising mistakes that cause mutations.

Rebecca Taylor rtaylor@mrc-lmb.cam.ac.uk

Systemic control of proteostasis and ageing. We are investigating the ways in which neurons detect stress, the means by which stress responses are communicated between cells, and how interventions in this process might be utilised to treat disease.

Christopher Russo crusso@mrc-lmb.cam.ac.uk

Atomic resolution imaging of biological specimen by electron cryo-microscopy. We aim to improve cryo-preparation and imaging methods to the point of using the electron microscope to image the atomic resolution structure of purified macromolecular complexes.

Katja Röper kroeper@mrc-lmb.cam.ac.uk The cytoskeleton in tissue morphogenesis. We investigate how the formation of epithelial tissues is driven by cellular and molecular changes, with a particular focus on the role of the cytoskeleton and its regulators during these processes.

William Schafer wschafer@mrc-lmb.cam.ac.uk

Cellular and molecular mechanisms of behaviour. We try to elucidate the mechanisms by which nervous systems process information and generate behaviour, and the cellular and molecular basis of sensory transduction and neuromodulation.

Julian Sale jes@mrc-lmb.cam.ac.uk Vertebrate mutagenesis and DNA damage tolerance. We aim to understand how impediments to DNA replication lead to mutation and to changes in the epigenetic signals that control gene expression.

Sjors Scheres scheres@mrc-lmb.cam.ac.uk

Visualising molecular machines in action. We develop data collection and processing methods for cryo-EM structure determination, and use these to understand how macromolecular machines work.

'Discoveries cannot be planned.They pop up, like Puck, in unexpected corners.'

Max Perutz

DIVISION KEY: CELL BIOLOGY | NEUROBIOLOGY | PNAC | STRUCTURAL STUDIESResearch Groups

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LMB Nobel Prizes

2018 Greg Winter

2017 Richard Henderson

2013 Michael Levitt

2009 Venki Ramakrishnan

2002 Sydney Brenner, Bob Horvitz, John Sulston

1997 John Walker

1984 César Milstein, Georges Köhler

1982 Aaron Klug

1980 Fred Sanger

1962 John Kendrew, Max Perutz

1962 Francis Crick, James Watson

1958 Fred Sanger

MRC LMB

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Babraham Park & Ride,Haverhill, M11

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MRC Laboratory of Molecular BiologyFrancis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK

Tel: +44 (0) 1223 267000 Fax: +44 (0) 1223 268300email: enquiries@mrc-lmb.cam.ac.uk Web: www2.mrc-lmb.cam.ac.uk

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CELL BIOLOGY NEUROBIOLOGY PNAC STRUCTURAL STUDIES

EditorsCristina RadaDavid Christensen

Design | PhotographyLMB Visual Aids

February 2019