Research Highlights Come Learn about our School's Research Dr. Ruben Hervas Millan What underlies the making of a memory?
Proteins, the penultimate output of the genome, are the workhorses in the cell. Normally, any given protein function is determined by its three-dimensional structure (fold/shape), the ultimate and functional genome output, which emerge from a complex biochemical process – the protein folding. Among many different protein folds, the amyloid fold corresponds with an aggregated protein state characterized by a filamentous morphology and specific structural attributes. Remarkably, in the human nervous system, amyloids are generally considered an unintended byproduct and are associated with various neurodegenerative diseases, including Alzheimer's or Parkinson’s. However, although structurally related, a different type of amyloids, known as functional amyloids, have been proposed to participate in an array of physiological processes in humans, including pigmentation, the storage of peptide hormones, antimicrobial responses, regulated necrosis, animal development or even memory persistence, among others.
Although our understanding of the principles that govern pathological amyloid aggregation is increasing, how amyloids could be functional entities remains poorly
understood. This is due, in part, to the lack of high-resolution structural information of functional amyloids isolated from their endogenous environment. Thus, the coupling of structural information with orthogonal data, such as activity tests or animal models to test the consequences of amyloid formation and disruption, may unravel new biological mechanisms. In our lab, we are interested in elucidating the structure, using electron cryo-microscopy, and function of amyloids implicated in memory consolidation & animal development. We anticipate that studying the structure of endogenous amyloids could offer insight into the functional consequences of amyloid formation in vivo and into how organisms regulate amyloid
assembly-disassembly to restrict their activity in time and space. Also, understanding differences between functional and pathological amyloids should help us to understand why amyloids are often associated with human diseases, and eventually how protein aggregation-based diseases, such as Alzheimer´s, might be treated.
Dr. Ruben Hervas Millan’s webpage
We need to eat and drink to survive, and so do our cells. To remain productive, cells consume nutrients like sugars, fats, and amino acids and convert them into energy through the mitochondria. While our cells can change their nutrient preferences to ensure their survival, this metabolic elasticity is not without cost. The price of nutrient loss is especially evident in immune cells — our fighters against cancer and infections. Dr. Heidi Ling’s Lab is performing investigations at the interface between the historically distinct disciplines of immunology and metabolism. We specialise in understanding the metabolism of CD8+T cells — killers of malignant cells and foreign invaders. These cells are particularly sensitive to metabolic changes, and glycolysis — the breakdown of glucose for energy, is critically important for CD8+T cell effectiveness. Dr. Heidi Ling Synergising immunity and metabolism to understand diseases
HL Lab is interested in metabolic disruptions during chronic inflammatory diseases, such as cancer and Type 2 diabetes (T2D). We investigate how the nutrient landscape in such conditions undermines the protective function of CD8+T cells, and aim to restore their functions through innovative treatments. Recently, we found that in cancer, CD8+T cells were signalled to shift away from glucose, their preferred metabolic fuel, to fatty acids. This metabolic switch weakened their anti-tumour activity and severed as a barrier to effective cancer immunotherapy. Our other line of research focuses on T2D, where glucose intolerance is evident in all cells including immune cells. Clinical data has associated T2D with an increased vulnerability towards respiratory viral infections e.g. COVID19. We are currently addressing this link through the angle of T cell metabolism.
Dr. Heidi Ling's webpage
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