two main steps: extraction of inclusion bodies from the bacteria followed by the solubilisation of the purified inclusion bodies. Solubilisation of inclusions bodies often involves treatment with denaturing agents, such as urea or guanidine chloride at high concentrations, to de-aggregate the collapsed proteins. Renaturation follows the treatment with denaturing agents and often consists of dialysis and/or use of molecules that promote the refolding of denatured proteins (including chaotopic agents and chaperones). Pseudo-inclusions Pseudo-inclusions are invaginations of the cytoplasm into the cell nuclei, which may give the appearance of intranuclear inclusions. They may appear in papillary thyroid carcinoma. Diseases involving inclusion bodies Inclusion body diseases differ from amyloid diseases in that inclusion bodies are necessarily intracellular aggregates of protein, where amyloid can be intracellular or extracellular. Amyloid also necessitates protein polymerization where inclusion bodies do not. Preventing inclusion bodies in bacteria Inclusion bodies are often made of denatured aggregates of inactive proteins. Although, the renaturation of inclusion bodies can sometimes lead to the solubilisation and the recovery of active proteins, the process is still very empirical, uncertain and of low efficiency. Several techniques have been developed over the years to prevent the formation of inclusion bodies. These techniques include: The use of weaker promoters to slowdown the rate of protein expression The use of low copy number plasmids The co-expression of chaperone (such as GroES-GroEL and DnaK-DnaJ-GrpE) The use of specific E. coli strains such as (AD494 and Origami) Fusing the target protein to a soluble partner Lowering the expression temperature See also Adult polyglucosan body disease Birbeck granules Ferruginous body JUNQ and IPOD Maltose-binding protein Nuclear bodies Orthopoxvirus inclusion bodies P-bodies Reinke crystals Stress granules References Biotechnology Blood Virology