When the first multicellular organisms evolved, their cells needed to communicate with each other to control their growth and development.
The deposition of misfolded proteins is a central characteristic of many devastating diseases including neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis and prion diseases. In principle, improving the cells’ ability to deal with misfolded proteins should reduce the pathology in these diverse neurodegenerative diseases.
The first X-ray crystal structure of the motor domain of cytoplasmic dynein, a protein that uses the cellular energy from ATP to walk along microtubule tracks that run throughout the cell, has been solved.
Cytoplasmic dynein moves numerous cargos around the cell including proteins and RNAs that set up the cell polarity, membraneous organelles, aggregated proteins that are toxic unless collected and disposed of, and even whole nuclei.
Amyotrophic lateral sclerosis (ALS) is caused by the progressive dysfunction of specific nerve cells that control muscle movement. It belongs to a group of devastating neurodegenerative diseases including Alzheimer’s, Parkinson’s, Huntington’s and prion diseases. Each disease is caused by the progressive accumulation of specific proteins in an aberrant, misfolded shape. The formation of the protein deposits is somehow toxic to nerve cells but why and how they initially form is unclear.
A group led by KJ Patel from the LMB, together with collaborators at the Wellcome Trust Sanger Institute and CRUK Cambridge Research Institute (CRI), have developed the first model for the human genetic illness Fanconi Anaemia (FA). This genetic condition results in abnormal development, bone marrow failure and a huge lifetime risk of developing cancer. At present the only long-term treatment for FA is bone marrow transplantation.
In a recent issue of Nature, the groups of Chris Tate and Andrew Leslie in the LMB’s Structural Studies Division, in collaboration with Gebhard Schertler now at the Paul Scherrer Institut, Switzerland, have reported the determination of the structures of the β1 adrenergic receptor (β1AR), a GPCR, when bound to four different clinically relevant agonists.
The social amoeba Dictyostelium discoideum is used widely in the laboratory as a convenient ‘model organism’ to help discover, among other things, how cells move, and how they fight bacterial infection. In the soil under your feet and in forest leaf litter, where it normally lives, this organism also goes through an enigmatic sexual cycle.
Landmark research led by Dr Leo James from the LMB’s PNAC Division has discovered that antibodies can fight viruses from within infected cells. This finding transforms the previous scientific understanding of our immunity to viral diseases like the common cold, ‘winter vomiting’ and gastroenteritis. It also gives scientists a different set of rules that pave the way to the next generation of antiviral drugs.
Dr Venki Ramakrishnan’s lab from the LMB’s Structural Studies Division have uncovered the molecular mechanism by which toxins such as ricin and alpha-sarcin inhibit protein synthesis in cells. It was known that these toxins act on a highly conserved RNA loop in the ribosome, the molecular machinery which synthesises proteins in both prokaryotic and eukaryotic cells.
Researchers led by Dr Bazbek Davletov at the LMB have developed a new method of joining and rebuilding molecules in the laboratory and have used it to refine Clostridium botulinum neurotoxin type A (more commonly known as botox). This new approach will enable researchers to improve its use as a treatment for diseases such as Parkinson’s, cerebral palsy and chronic migraine. It also opens up new avenues to develop new forms of the toxin which could be used as a method of long-term pain relief.