Mini-Science 2015 – “Biomimicry and the synthetic synapse”
At the conclusion of each Mini-Science lecture, audience members submit their questions to the evening’s presenter. If there is not enough time to answer them all on the spot, some of the other unanswered questions are sent to the presenter for posting here. Here are questions from Professor Timothy Kennedy’s lecture “Biomimicry and the synthetic synapse” (March 25, 2015).
Q: How can the cell respond to an unnatural enantiomer of an amino acid? Wouldn’t it not be “programmed’ to deal with an non-naturally occurring molecule? PLL (Polylysine ligament cells) vs PDL (Periodontal ligament cells).
A: The response of the cell depends on what component of the polymer it is responding to. In the case of PLL and PDL, we think that the cell is simply responding to the positive charge of the lysine amino acid, with the shape of the polypeptide backbone not being particularly relevant. Importantly, that this is not always the case. There are many examples of protein-receptor interactions that are strongly dependent on the 3D folded shape of the ligand.
Q: Can you measure the amount of netrins in a brain? Can you tell when they are lacking?
A: Yes we can measure the amount of netrin in a brain, but unfortunately we can’t currently do this in a living brain. We are examining the levels of netrin present in post-mortem human samples and in animal models of human neurodegenerative disease. We are very interested in the possibility that the levels of the various members of the netrin family may change as part of a disease process. We are also interested in the possibility that netrin could be added to certain cells, perhaps slowing the progression of a disease.
Q: You study rat brains to understand the way synapses and neurons work. What are the biggest challenges to ‘scaling up’ to real human brains?
A: The cellular and molecular biology of synapses in the mouse and rat brain are very similar to a human brain. A lot has been done and there is much more to do. Similarly, when considering the function of neural circuits, again the rodent brain is extremely useful for working out how groups of neurons work together to process information. A substantial challenge is to generate and interpret mouse models of complex human neural diseases, with psychiatric disorders being an extreme examples. Even when a particular gene mutation has been implicated in humans and an appropriately genetically modified mouse generated, a mouse will not volunteer the information that it is depressed or experiencing hallucinations. Even so, a substantial number of well characterized behavioural tests have been generated that are being used to study mouse models of human disorders like autism, schizophrenia, etc.
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