A Heart Attack After Lunch (Thankfully in a Dish)

The session kicked off with a heart attack (I hope the food did not have too much cholesterol!). However in this case,  Adam Engler at UCSD, has developed assays to cause heart attack in a dish in his laboratory. They designed a material, which can increase in stiffness in a step wise fashion. This helps them to assay how dynamically changing matrix affects heart development and may lead to a heart attack in older hearts. They then looked at the 9p21, a large non-coding RNA. Single nucleotide polymorphisms in this RNA increases the risk of familial heart attack. They show that indeed this ncRNA can regulate connexin expression levels. Alteration in these levels leads to an increased risk of heart attack. This is such a fantastic model to study heart attacks in vitro. Heart being a mechanical tissue, these materials now provide amazing ways to look at those aspects in a dynamically changing mechanical landscape.

Next Krystyn Van Vliet from MIT attempted to address an important issue — why  mesenchymal stem cells (MSCs) are not used for any FDA approved therapy.  She postulates that this is because of heterogeneity in the stem cell population. To make the cells segregate reliably into distinct populations based on cell diameter, cell stiffness and nuclear fluctuations, they build a microfluidics based device. They show that based on these three features, they can separate the cells that are still stem-like and have not exited the cell cycle. Moreover, this device is now in clinical trials in Singapore and provides a promising way to use MSCs for reliable therapeutic purposes with the major ill effects of the same.

This was followed by a talk by Yunn Hwen Gan from NUS. Her lab studies Burkholderia pseudomallei, a pathogen that causes melioidosis. This bacterium infects mammalian cells and, using a typeIII/IV secretion system, it leads to cell fusion and form large multinucleate cells. This induces interferon 6 and cytosolic DNA, which helps mount an immune response. The interesting part of their discovery was that, in this bacterium, unlike other bacteria, it uses the secretion system once it has infected the host and is inside the host cell. This provides interesting ways to think about therapy.

The next talk of the session was by Samuel Safran from Weizman Institute. He educated me about some very important theories on how holes close. This becomes particularly relevant when cells are challenged to squeeze through narrow pores and this may create holes in the nuclear membrane. The hole closing would depend on line tension (leading to shrinkage) and lateral stress (growth). Outflow of liquid from the hole in a 3D system would also contribute to this. The flow of fluid – chromatin in the case of nucleus, that is very viscous- would change the dynamics of hole closure. This is an important problem, as inability to close the holes, would be detrimental to the cell.

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