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| Location |
Cambridge, UK |
| Type |
Research Institute |
| Website |
https://www.mrc-lmb.cam.ac.uk/ |
| Focus Areas |
[Tau](//tau-pathology), [Alpha-synuclein](/proteins/alpha-synuclein), Protein aggregation |
| Departments |
MRC Laboratory of Molecular Biology |
University of Cambridge - MRC LMB is a world-renowned research institute located in Cambridge, UK. The MRC Laboratory of Molecular Biology (LMB) is one of the world's most influential biomedical research centers, having produced multiple Nobel Prize winners. While famous for fundamental discoveries in molecular biology, the LMB has made critical contributions to understanding the molecular basis of neurodegenerative , particularly in protein aggregation central to Alzheimer's and Parkinson's .
The institution hosts 1 researcher tracked in the NeuroWiki database and maintains 1 department dedicated to neuroscience research. The research programs span Tau, Alpha-synuclein, and Protein aggregation, contributing to both basic science understanding and translational approaches for neurodegenerative conditions.
¶ History and Milestones
The MRC LMB has a distinguished history of groundbreaking discoveries in molecular biology.
Key Historical Milestones:
- 1947: MRC LMB established as the unit for Research in Cell Biology
- 1962: Move to Cambridge, became the MRC Laboratory of Molecular Biology
- 1972: First structure of an antibody (immunoglobulin)
- 1997: Discovery of prion protein structure
- 2013: Cryo-EM revolution in structural biology
- 2017: Breakthrough in tau filament structures
- Cryo-EM structures of tau filaments from AD and CTE
- Alpha-synuclein fibril structures from Parkinson's disease
- Prion protein misfolding
- Molecular of aggregation
- Strain diversity in protein aggregates
- Seeding and propagation
- Structure-based drug design
- Antibody targeting of pathological conformers
- Small molecule aggregation inhibitors
¶ Notable Discoveries and Contributions
- Bretscher & Rothman (2013): Vesicle trafficking
- Kendrew & Perutz (1962): Protein structure (hemoglobin)
- Porter & Edelman (1972): Antibody structure
- Tau Filament Structures: First atomic structures of tau filaments from AD brain (2017)
- Alpha-Synuclein: Cryo-EM structures of Lewy body fibrils
- Prion Protein: Structural basis of prion propagation
- Cryo-electron microscopy methodology
- Image processing algorithms
- Single-particle reconstruction methods
| Researcher |
Focus Areas |
| Michel Goedert |
Tau, Alpha-synuclein, Protein aggregation |
| Sjors Scheres |
Cryo-EM, Structural biology |
| Hilary Coller |
Autophagy, Protein homeostasis |
¶ Funding and Resources
- MRC Core Funding
- Wellcome Trust Investigator Awards
- European Research Council (ERC) Grants
- Cryo-EM Facility: Multiple Titan Krios microscopes
- Protein Production Facility: Bacterial and mammalian expression
- Computing Infrastructure: Large-scale image processing
- Fitzpatrick et al., Nature (2017) - Cryo-EM structures of tau filaments from Alzheimer's disease brain
- Guo et al., Nature (2018) - Structure of alpha-synuclein fibrils from Parkinson's disease brain
The MRC LMB maintains global research partnerships:
- Wellcome Trust: Major UK funding
- European Research Council: EU collaborations
- International Structural Biology Networks
- Cryo-EM: New structural discoveries
- Amyloid fibril strains: Understanding diversity
- Therapeutic antibodies: Structure-based design
- Basic mechanism discovery
- Method development
- Translation to therapeutics
¶ Impact and Recognition
- 12 Nobel Prizes awarded to LMB scientists
- Fundamental discoveries in molecular biology
- Revolutionary imaging technologies
- Disease mechanism understanding
- Cryo-EM Suite: Multiple Titan Krios microscopes
- X-ray Crystallography: Protein structure determination
- NMR Spectroscopy: Solution structure analysis
- Protein Expression: Bacterial and mammalian systems
- Protein Purification: FPLC and chromatography
- Biophysical Analysis: SPR, ITC, AUC
- High-Performance Computing: Large-scale calculations
- Image Processing: EM processing software
- Molecular Dynamics: Simulation capabilities
- PhD Program: 4-year doctoral training
- Postdoctoral Fellowships: Advanced research training
- Visiting Scientists: International collaborations
- Spin-out companies
- Patent licenses
- Industry partnerships
- High-impact journals
- Method publications
- Disease mechanism papers
The MRC LMB has pioneered the application of cryo-electron microscopy to neurodegenerative disease research:
- Tau Filament Structures: First atomic structures of tau filaments from Alzheimer's disease brain (2017, Nature)
- Alpha-Synuclein Fibrils: Structures of Lewy body fibrils from Parkinson's disease brain
- TDP-43 Aggregates: Structures of ALS-associated protein aggregates
- Prion Protein Strains: Structural basis of prion strain diversity
Understanding the molecular basis of amyloid formation:
- Amyloid-beta Aggregation: Mechanism of oligomer and fibril formation
- Islet Amyloid Polypeptide: Diabetes-related amyloid research
- Cross-Beta Structure: Common structural features of amyloid fibrils
Research into cellular systems that handle misfolded :
- Molecular Chaperones: Protein folding and quality control
- Autophagy: Lysosomal degradation pathways
- Proteasome System: Ubiquitin-proteasome degradation
The LMB has been instrumental in developing cryo-EM technology:
- Direct Electron Detectors: Gatan K2 cameras and similar technologies
- Image Processing Software: RELION and other packages
- Single Particle Analysis: Methodology development
- Tomography: Cellular tomography approaches
- X-ray Crystallography: Traditional structure determination
- NMR Spectroscopy: Solution-state structural studies
- Mass Spectrometry: Proteomics and post-translational modifications
- Fluorescence Microscopy: Live cell imaging
Structural insights are enabling rational drug design:
- Antibody Development: Structure-based design of therapeutic antibodies
- Small Molecule Inhibitors: Aggregation inhibitors based on structural knowledge
- Peptide Therapeutics: Designed peptides targeting aggregation
- Fibril Detection: Ultrasensitive methods for aggregate detection
- Strain Typing: Distinguishing between different aggregate strains
- Biomarker Development: Fluid-based diagnostics
¶ Training and Education
- PhD Program: 4-year doctoral research training
- MPhil Option: Master's by research
- Rotation System: Exposure to multiple techniques
- Independent Research: Development of independent projects
- Technique Training: Comprehensive methodological training
- Career Mentorship: Guidance for career progression
- Short-Term Visits: Collaborative projects
- Sabbaticals: Extended research stays
- Workshops: Technique-specific training
Understanding the structural diversity of protein aggregates:
- Strain Biology: Different structural forms have different properties
- Transmission: Understanding cross-seeding and templated aggregation
- Strain-Specific Therapies: Targeting specific strains
Moving from in vitro to cellular and organismal models:
- Cellular Models: Neuronal cell models of aggregation
- Organoids: Brain organoid models
- In Vivo Models: Animal models with humanized sequences
Integrating computation with structural biology:
- Molecular Dynamics: Simulation of aggregation processes
- Machine Learning: Prediction of aggregation propensity
- AlphaFold Applications: Structure prediction for aggregation