Coffee break over, lets get back to some more interesting science.
It started with Shyni Varghese from UCSD telling us about fibrosis – a condition where the matrix stiffens. Using a genome wide screen, they identified several players that might be important for inflammation and fibrosis. They found fibulin5 to be important in progression of fibrosis. It is associated with elastin and is not essential for development and growth (as tested in knockout mice). So, it appears to be a great target for therapeutics.
This was followed by a talk from Cytovale, a three year old spin off company from Dino di Carlo’s lab. The company is based on the idea that nuclear mechanics can be used as a marker to identify disease states in the cells. One major disease they target in this first phase is sepsis, which leads to death in a large number of patients due to late detection. The major detection marker now is production of lactate. They plan to aid early diagnosis and hence better prognosis by using features in the nucleus as a biomarker. They have developed a PDMS device to stretch the tissues cells reliable and reproducibly. This device is called deformability cytometry cartridge. Using machine-learning algorithms including stochastic nearest neighbor, principle component analysis, DISNEY (developed in Columbia university) they identify a dozen features in the nucleus, which can separate healthy cells from unhealthy ones. The whole workflow takes about 10 minutes, hence is a fast method of diagnosis. With a customizable chip, they hope to use this for many other diseases and would like to hear and collaborate with new researchers to find out ways of enhancing their technology and developing it to diagnose other diseases and have other applications in research laboratory.
Next talk was by Natalie from Sydney where she studies the role of Calapin in membrane repair. They rupture the membrane by shooting it with silicon bullets of about 4um using a gene gun. Using this they identified a mutant of dysferlin, a calcium responsive gene that upon calpain mediated cleavage forms a synaptotagmin like mini dysferlin, which aids in vesicle fusion to the membrane in order to repair it.
The final talk of this session was by Victor Ma from Salaita Lab @ Emory. They use DNA based tension gauge to measure the forces of T cell binding to its receptor. Using this assay they are able to show that stronger binding of the TCR-ligand complex leads to a signal for the T cells to signal. This is a way to avoid signaling upon weak binding and increase specificity of T cell signaling.
Action packed session I must say! Lets get some lunch!