iBiology Podcast

All general anesthetics act in the brain stem region to induce slow brain oscillations. Brown shares EEG spectrograms that clearly show that the brain response to anesthesia varies with age. Younger brains show strong oscillations while those of older brains show weaker oscillations.  Interestingly, not all brains “age” at the same rate. By using EEG spectrogram to visualize brain dynamics, anesthesiologists can optimize drug dosage for individual patients. Brown closes his talk by presenting recent research suggesting that it may be possible to “turn the brain back on” after general anesthesia as a way to speed patient recovery.

What happens to your brain when you are under general anesthesia? Dr. Emery Brown explains that under general anesthesia your brain is not turned off but is very dynamic. Electrical oscillations in the brain can be recorded using an electroencephalogram (EEG).  Brown shows how oscillations induced by anesthesia interfere with normal communication between different regions of the brain. By following oscillations of different frequencies, it is possible to monitor and adjust a patient’s level of unconsciousness under anesthesia.

In her third talk, Braybrook switches gears and highlights work from her lab on cell walls found in brown algae (seaweed).  Although seaweed cell walls have much in common with plant cell walls, they do have some differences. Seaweed cell walls contain much less cellulose than plants, in fact, most of the wall is made of the gel matrix material, alginate. Braybrook’s lab studies the Fucus seaweed embryo to learn how changes in the rigidity or fluidity of the gel matrix impacts cell expansion patterns during development.

For a plant seedling to grow upwards and out of the soil so it can begin to photosynthesize, it must grow more in length than in width. Growth that occurs in one direction more than in another is called anisotropic growth.  How do cells do this? In plants such as Arabidopsis, almost all of the initial increase in plant length or height is due to anisotropic growth of cells rather than cell division. In her second talk, Braybrook explains how her lab is using this system to study the role of cell wall components in determining anisotropic growth.

Cell walls are found throughout the tree of life (even in some animals!) and in most cases they serve similar functions of strengthening and protecting cells.  Dr. Braybrook’s research focuses on cell walls found in multicellular organisms such as plants and brown algae. In her first talk, Braybrook explains that cell walls are made of cellulose which forms long strong fibers, a gel matrix such as pectin or alginate in which the cellulose is embedded, and cross-links such as hemicellulose or lignin that provide strength and hold the wall together. By improving our understanding of cell wall structure and biology, Braybrook’s research may help facilitate our use of plants and seaweed for biofuels and other products.

Dr. J. Michael Bishop tells us the story of his Nobel Prize-winning discovery of cellular proto-oncogenes. Bishop was studying how the Rous Sarcoma Virus (RSV) causes cancer in chickens by expressing the viral protein called Src. Together with Dr. Harold Varmus, Bishop discovered that the chicken genome normally expresses a homolog of the viral Src protein that they called cellular-Src (c-Src). This finding led them to the remarkable conclusion that RSV had incorporated a mutated oncogene version of the normal chicken c-Src protein, and, provided the first evidence that mutations in our own genes can be linked to cancer development.

In his second talk, Dr. Benfey dives even further into the cellular differentiation pathway of plant roots. He provides an explanation of the signaling pathway that activates positive feedback and feed-forward loops that impact the organization of cells as the root develops. He also covers how roots function as they spread through soil and how a chemical compound his lab identified can help roots grow through saline soil.

In his first talk, Philip Benfey gives an overview of root genetics and his work to identify genes that are involved in the process that takes a stem cell to a differentiated tissue. He explains how mutant Arabidopsis plants with shorter roots helped his lab understand how specific genes are expressed in plant roots, and how these genes affect root function. He reveals how a protein encoded by a gene called SHORTROOT moves from the vascular tissue to the endodermis to induce expression of another gene called SCARECROW. This whole complex is the on-off switch that causes certain root cells to divide and differentiate properly. Benfey also talks about how these genes can be used to change cell identity.

In Part 2 of his talk, DeBose-Boyd introduces a rare genetic disorder known as Schnyder Corneal Dystrophy (SCD). SCD is characterized by accumulation of cholesterol in the corneas of affected individuals, indicating that the genetic defect in SCD may affect cholesterol synthesis. Mutations in the UBIAD1 gene cause SCD – therefore, DeBose-Boyd’s lab sought to understand the role of UBIAD1 in regulation of cholesterol metabolism. They found that UBIAD1 acts as a sensor for levels of the metabolite GGpp, which enhances sterol-mediated ERAD of HMG CoA reductase. In the presence of GGpp, UBIAD1 releases HMG CoA reductase, leading to its proteasomal degradation. DeBose-Boyd’s lab also discovered a fascinating spatial regulation of UBIAD1, whereby binding of UBIAD1 to GGpp causes UBIAD1 to accumulate in the Golgi apparatus and away from HMG CoA reductase in the ER. Finally, his group found that the SCD-associated mutation N102S in UBIAD1 inhibits the interaction between UBIAD1 and GGpp, such that mutant UBIAD1 is unable to translocate from the ER to the Golgi in the presence of high GGpp.

Regulation of cholesterol synthesis is very important: cholesterol is a component of cell membranes and a precursor of steroid hormones and bile acids, yet high levels of cholesterol can be toxic to cells and can contribute to heart disease. Cells in our body obtain cholesterol one of two ways – by taking it up from the bloodstream (via low-density lipoprotein or LDL) or by synthesizing it intracellularly. In Part 1 of his iBioSeminar, Dr. Russell DeBose-Boyd provides an overview of cholesterol regulation with a focus on HMG CoA reductase, the rate-limiting enzyme of cholesterol synthesis. He describes how the effects of statins, drugs prescribed to lower LDL in the blood, are blunted due to the disruption of feedback control of HMG CoA reductase. In the presence of sterols, HMG CoA reductase protein stability is decreased. This sterol-accelerated degradation of HMG CoA reductase is dependent on the enzyme’s membrane domain in a process known as ER-associated degradation (ERAD). DeBose-Boyd describes his lab’s contributions to a model of HMG CoA reductase ERAD in which polyubiquitination of the enzyme in response to sterols is mediated by two proteins, Insig-1 and Insig-2, leading to its ERAD by the 26S proteasome.