Figuring out how diverse types of cells in the human body function, communicate, and respond to external stimuli is the focus of the Cell Information Systems (CIS) research theme in 平特五不中鈥檚 Life Sciences Complex (LSC). Working with a range of sophisticated research tools, including state-of-the-art microscopy, electrophysiology and mass spectrometry, the group鈥檚 researchers study membrane proteins in live cells, tissues and whole animals, and their roles in a variety of diseases including cystic fibrosis, cardiac arrhythmias as well as neurodevelopmental and neurodegenerative pathologies (intellectual disability, Fragile X, Alzheimer鈥檚 disease, pain).

, Theme Leader for CIS, says the LSC's inception was responsible for attracting some of the best molecular and cell biologists from all over the world to 平特五不中. The easy access to cutting-edge equipment housed within the Complex and a highly collaborative environment have been key to the LSC's continued success in bringing in promising young researchers. "These recruitments would not have been possible without this Complex," says Dr. Shrier, noting that its shared lab space has already facilitated many fruitful collaborations. "It brought people together."

Three big breakthroughs in Cell Information Systems

1. Understanding the inner workings of brain circuits: The human brain is packed full of neurotransmitter receptors which are signalling proteins critical in coordinating the activity of neurons and brain circuits. Dysregulation of their activity leads to human disease, such as autism in young infants, schizophrenia and epilepsy in adults as well as Alzheimer鈥檚 disease and Parkinsonism in the elderly. Recent work from has identified a critical role of a family of 鈥渉elper鈥� proteins that modify an abundant class of neurotransmitter receptors, called AMPA receptors. Since these AMPA receptor auxiliary subunits are expressed in different brain regions, the selective targeting of these receptor complexes may be beneficial in developing novel therapeutic compounds with better specificity and thus fewer side effects for patients. In their recent study, they have made an important step forward by identifying how AMPA receptors interact with auxiliary subunits. These findings not only provide valuable insight into the molecular underpinnings of neuronal circuits that underlie human behaviour but also provide an understanding into brain disease.

2016 Mar 16;89(6):1264-1276. . Epub 2016 Feb 25.

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2. Combined therapeutic approach for Cystic Fibrosis: Current treatments for cystic fibrosis (CF) are unable to combat the most common root cause of the disease: defects in the folding of the newly synthesized mutated cystic fibrosis transmembrane conductance regulator (CFTR), 螖F508-CFTR, to attain its proper three-dimensional shape. This mutation is responsible for hampering the body's ability to produce the appropriate levels of water and salt in the linings of the gut and lungs, leading to epithelial stickiness and frequent infections. New findings from Dr. Gergely Lukacs's lab suggest that using a cocktail of novel compounds to target multiple structural defects can correct the folding defects of 螖F508-CFTR and improve epithelial function. The findings could lead to new therapeutic pathways for as many as 50% of CF patients.

Nature Medicine 2018 Oct 8. . [Epub ahead of print]

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3. A new form of intellectual disability: , in collaboration with international scientists, has identified a new form of nonsyndromic intellectual disability characterized by moderate to severe cognitive dysfunction, with brisk reflexes, hypotonia, muscle weakness and bilateral clinodactyly. The findings identified a recurrent genetic defect in the gene called SLC9A7, which is located on the X chromosome and regulates Golgi pH homeostasis and glycosylation of proteins. They have proposed that disruption of these cellular processes may underlie the cellular pathophysiology and neurodevelopmental deficits associated with this particular nonsyndromic form of X-linked intellectual disability.

Human Molecular Genetics (in press)