iBiology Videos

Why do females fight? For over a century, biologists thought that female aggression was uncommon in the animal kingdom. In this lecture, Dr. Eleanor Bath dispels that notion and shows that female aggression in fruit flies increases after mating. More specifically, she shows that semen and a small protein in the male ejaculate lead to increased female aggression in Drosophila melanogaster.

What is the involvement of microRNAs in the inflammatory response? In this seminar, Dr. David Baltimore shows that the expression of three microRNAs (miR-132, miR-146, and miR-155) increase upon activation of the inflammatory pathway. Baltimore characterizes these microRNAs and shows how they are involved in the precise tuning of the inflammatory response.

Ashcroft expands on what is known about the KATP channel and its role in insulin secretion.  It is an octomeric complex composed of 4 Kir6.2 subunits and 4 SUR1 subunits. ATP binds to both proteins, and changes in metabolically generated ATP couple metabolism to KATP channel activity. Functional studies showed that the KATP channel mutations found in neonatal diabetes impair the ability of ATP to close the channel and stimulate insulin release.  This suggested that drugs that could directly close the KATP channel would stimulate insulin release and might be a good therapy for neonatal diabetes. Sulfonylurea drugs were already known to directly close the KATP channel and have been safely used to treat type 2 diabetes for many years. Based on this knowledge, many patients with neonatal diabetes have now switched from insulin injections to oral sulfonylurea drugs. This has resulted in much better glucose control.  Ashcroft goes on to explain how insights from studying neonatal diabetes have also led to a better understanding of the impact of chronic hyperglycemia in type 2 diabetes.

Dr. Norma Andrews overviews the mechanisms of cellular plasma membrane repair. As she describes, a lesion is followed by a Ca2+-dependent movement of vesicles to the plasma membrane. By studying how the Trypanosoma cruzi parasite enters the cell, Andrews’ laboratory discovered that an increase of intracellular calcium was triggering lysosomal fusion to the plasma membrane. This unexpected observation allowed them to conclude that upon an injury to the plasma membrane, a Ca2+ influx induces lysosomal exocytosis mediated repair. This research demonstrates that lysosomes are not only responsible for the degradation of material that comes inside the cell through endocytosis, but also have an important role in plasma membrane repair.

Andrews further explains how Ca2+-dependent exocytosis of lysosomes aids membrane repair. Her laboratory showed that after lysosomal exocytosis, an injury to the plasma membrane would also trigger a Ca2+-dependent endocytosis that is required for the repair mechanism. Andrews laboratory showed that lysosomes release the enzyme acid sphingomyelinase (ASM) which induce the endocytosis required for plasma membrane repair.

Injecting adult stem cells into the bloodstream could help regenerate tissue damaged by heart attacks. For this to happen, circulating stem cells need to exit blood vessels and reach the damaged tissue. While scientists knew that circulating stem cells are able to exit the bloodstream, how they did it was a mystery. In this lecture, Tyler Allen describes angiopellosis, a new way for circulating stem cells exit blood vessels when injected into the blood for therapies.

This talk is part of the Young Scientist Seminars, a video series produced that features young scientists giving talks about their research and discoveries.

Many of us are used to seeing cartoons of cells with organelles shown as static, isolated structures. The endoplasmic reticulum (ER) is often shown looking like a stack of pancakes pushed up against the nuclear envelope. In her first talk, Dr. Gia Voeltz explains that recent advances in light microscopy have given us a very different view of organelles and their interactions. The ER is, in fact, an expansive, and highly dynamic, network of tubules that spreads throughout the cell.  It interacts with other organelles such as the plasma membrane, endosomes, and mitochondria at points called membrane contact sites. Using beautiful fluorescent images and movies, Voeltz shows us that these ER membrane contact sites are important for many functions such as trafficking lipids and Ca2+ and determining where mitochondria divide and endosomes undergo fission. These exciting findings define a new cellular function for the ER.

Voeltz explains how her lab used a BioID strategy to identify some of the proteins found at membrane contact sites between the ER and endosomes; a difficult task given the transient nature of contact sites.  They were able to identify a number of proteins responsible for marking the timing and location of endosome fission and for recruiting the ER to the bud. Depleting these proteins blocked cargo sorting to the Golgi. Voeltz’ lab is now working to determine how much of this machinery is conserved in processes such as the mitochondrial 

Dr. Tom Rapoport explains that eukaryotic cells contain many membrane-bound organelles each of which has a characteristic shape and distinctive functions that are determined by specific proteins. Most proteins are made in the cytosol but must move to different cellular destinations.  Signal sequences on the proteins act as “zip codes” and direct protein sorting. Many proteins sort first to the endoplasmic reticulum (ER) before moving to other intracellular organelles or the plasma membrane. Rapoport explains that the Sec 61 channel in the ER membrane is key to protein sorting. Solving the structure of Sec 61 allowed Rapoport’s lab to understand how proteins are transported across the ER membrane and directed to their final destination.

The ER is a vast network that includes different domains with different functions. The rough ER is made of ribosome covered membrane sheets and is involved in protein translation.  The smooth ER consists of tubules and is important for lipid synthesis and Ca2+ transport. In his second talk, Rapoport explains how his lab identified several families of proteins needed to generate and maintain a tubular ER network. Using ultra-thin section microscopy, Rapoport and others also showed that stacked ER sheets are held together by helicoidal membrane connections that form a “parking-garage” like structure.