After a 4 month hiatus due to computer and website security issues, I am back. Today, I am going to dive back into the wonderful world of gut microbes. As I have mentioned in a previous post, the bacterial population in our intestines plays important roles in our general health. In fact, the genome of the bacteria in our gut is called our “metagenome”, which like our genome, encodes various genes and proteins that play complementary functions to those we already have. Studies have shown that people with chronic diseases, like inflammatory bowel disease and obesity, have an altered gut bacterial population compared to healthy individuals. Not surprisingly, since food passes through our intestines, it can affect the amounts and the types of bacteria that grow there.
Complexity of biological systems
With all the funds and manpower devoted to bioscience research for the last fifty years, we should have understood everything there is to understand in biology by now, but why not? The main reason is that biological systems are inherently complex, meaning that there are many interactions between the parts that make up the system. This is all fine and dandy if all these interactions are considered in every study, but truth to be told, most biologists only study the interaction that they are interested in due to time and resource constraints. I will illustrate two types of complexity below.
In Vivo Systems Analysis Identifies Spatial and Temporal Aspects of the Modulation of TNF-{alpha}-Induced Apoptosis and Proliferation by MAPKs (Lau et al., Science Signaling, 2011,4:ra16)
The traditional way to study biology is the so-called “bottom-up” or “reductionist” approach. For the most part, a scientist picks a subject of interest to study (a gene or protein or pathway), learns everything there is to know about it, and then tries to insert his or her findings back into the context of the bigger picture. The major assumption of this approach is that biological systems are built in a modular manner. That is, the gene/protein/pathway has only a few connections to the rest of biological system, such that it can be studied in isolation and its function can be plugged back into the “bigger picture” with relatively ease.
Telomere dysfunction induces metabolic and mitochondrial compromise (Sahin et al., Nature 2011, 470: 359-65)
One of the hot topics in biology today is the question of why we age. There are currently two major biological entities related to this issue that are being intensely studied: 1) a class of deactetylase proteins called sirtuins, and 2) telomeres. This paper is about the effects of the latter on aging.
p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis (Kirsch et al., Nature 327, 593-6, 2010)
Due to the recent nuclear power plant emergency in Japan, many people are concerned about the effects of radiation. Aside from increasing long term cancer risks, exposure to a high dose of radiation can cause acute symptoms, collectively known as radiation poisoning. Two of the most prominent symptoms are hematopoietic cell (aka blood cells) loss and gastrointestinal tract issues, both of which are caused by the killing of stem cells by radiation.
Melanomas acquire resistance to B-RafV600E inhibition by RTK or N-Ras upregulation (Nazarian et al., Nature 468, 973-7, 2010)
Have you ever wonder why cancer is so hard to cure? There are a few reasons. One is that unlike infections, cancer cells are derived from your own cells, and hence, can evade the immune system. Secondly, cells usually become cancerous by undergoing some sort of genetic mutation. The mechanism of mutation frequently involves defects in DNA damage response, resulting in DNA not being replicated correctly. Thus, cancer cells can change continuously via the same mechanism to evade therapies.
Bifidobacteria can protect from enteropathogenic infection through production of acetate (Fukuda et al., Nature 469, 543-7, 2011)
I actually want to talk about this paper today:
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43 (Maslowski et al., Nature 461, 1282-6, 2009)
Oncogene Addiction
Last time, I talked about targeted therapy for cancer. The main advantage of targeted therapy is that it should specifically kill cancer cells. However, it is widely known that cancer cells have evolved to be more hardy than normal cells. This is evident in their resistance to variety of cell death stimuli, and the fact that these cells can be taken out of the body and grown in artificial cell cultures (where normal cells cannot). So why do cancer cells die when only one specific protein is deactivated? One of the theories that explain the vulnerability of cancer cells is the theory of oncogene addiction.
Targeted Therapy
There are two traditional ways to treat cancer: 1) surgery to excise the cancer out of the body, and 2) chemo- and radiation therapy that kills rapidly dividing cancer cells. Different circumstances call for different treatments, but it is common nowadays to use some combination of the two. Obviously, these two options are not perfect. Surgical removal of the cancer mass is usually not complete, that is, a few tumor cells will be left behind causing relapse later on. Chemo- and radiation therapy can kill tumor cells, but also affect normal rapidly dividing cells in the body like hair follicles and the intestinal epithelium. There is a limit that the body can take before giving out completely.
Cell Polarity
Today, I am going to talk about the topic of cell polarity. Most people, even cell culture biologists, think of cells as blobs that will divide in all directions.
