Recent studies about molecular genetics SE 253 GROUP TASK REPORT BY: RAYYAN M. BATUAN AMINA A. ABANG NAJIYAH A. SIDIC 1. For stem cells, bigger doesn’t mean better By: Jette Lengefeld, introduction • It has been known since the 1960's that human cells grown in a lab dish enlarge as they become senescent--a nondividing cellular state that is associated with aging. • Every time a cell divides, it can encounter DNA damage. When this happens, division is halted to repair the damage. During each of these delays, the cell grows slightly larger. • Many scientists believed that this enlargement was simply a side effect of aging, but Amon lab(researcher) began to investigate the possibility that large cell size drives agerelated losses of function. introduction • In our stem cells which is among the smallest cells in our bodies that functions in replenishing our blood cells, these cells tend to enlarge when they get old, and when these cells enlarge, their functions are reduced or becomes abnormal by not producing blood cells which will cause to aging related diseases or aging of our cells to be rapid. methods First experiment: Use of two damaged DNA, one is uncontrolled and the other is controlled with rapamycin. These are injected to mice which stem cells are eliminated. Step 1: Step 2: DNA damage 1 (Uncontrolled) INJECTED DNA damage 2 (Controlled) Mice (own blood stem cells are removed) methods Second experiment: Use of genetic mutations (controlled) to stem cells of old mice Genetic mutations (Controlled) Old mice (stem cells) discussion In this study, in the first experiment, there are 2 DNA damage samples that is observed to study how size affects these stem cells. o The first DNA damage is uncontrolled which means this enlarged stem cell is continuing its size to grow larger, while the second DNA damage is controlled with the use of Rapamycin, a drug that can inhibit cell growth which means that this enlarged stem cell is preventing its size to grow and is being restored to its usual small size which makes them function properly and normally. discussion Rapamycin- is a drug that inhibit cell growth. It is now used to treat some cancers and to prevent organ transplant rejection, and has raised interest for its ability to extend lifespan in mice and other organisms. It may be useful in slowing down the enlargement of stem cells and therefore could have beneficial effects in humans. discussion o To compare these, the researchers measured the functionality of these two groups of stem cells by injecting them into mice that had their own blood stem cells removed. o When they tested the mice with rapamycin, beginning at a young age, they were able to prevent blood stems cells from enlarging as the mice got older. Blood stem cells from those mice remained small and were able to build blood cells like young stem cells even in mice 3 years of age (old age) for a mouse. o This allow the researchers to determine whether the transplanted stem cells were able to repopulate the mouse's blood cells. discussion o In the second experiment, they observed the naturally large stem cells they found in older mice by using genetic mutations (controlled) to reduce its size and be able to perform its function properly. results The researchers found out that the DNA-damaged and enlarged stem cells (uncontrolled) were unable to produce new cells. However, the DNAdamaged stem cells that were kept small (controlled) were still able to produce new blood cells. It is the same with using of genetic mutations, they also found out that to control the growth of stem cells of the old mice, they showed that if they induced those large stem cells to become small again, the cells regained their regenerative potential and behaved like younger stem cells. results This is an evidence supporting the model that size is important for functionality of stem cells. (The larger the stem cells, the more abnormality of its function) They concluded by suggesting that this relationship of cell size and function is conserved in stem cells, and that cellular size is a marker of stem cell function. results They also demonstrate the importance of size in another type of stem cells-intestinal stem cells. They also suggested that if we find drugs that are specific in making large blood stem cells smaller again, we can test whether this improves the health of people who suffers from problems with their blood systems like for instance in anemia, and a reduce immune system or may be even help people with leukemia. results Because of this study, it is also highly possible to treat cellular enlargement to delay aging and aging-related diseases (as the researchers are trying to explore for existing studies) 2. One way genetic mutations occur during formation of eggs and sperm By: The Sloan Kettering Institute (SKI) researchers introduction • The human life cycle starts with the union of two sex cells (also known as germ cells), a sperm cell from a father and an egg cell from a mother. The process is called fertilization that produces a zygote. • Both sperm and egg cells are produced in a type of cell division called meiosis. • The sex cells produced during meiosis are haploid cells because they contain only half the number of chromosomes. A haploid cell is represented with the symbol n. • As a result of the union of the haploid sperm cell(n) and a haploid egg cell(n), a diploid (2n) zygote is formed. the zygote contains two sets of chromosomes-one set from the father(n) and one set from the mother(n). • Thus, the zygote is a diploid cell(2n). introduction • In humans, one set of chromosomes is equal to 23 thus, the diploid zygote contains 46 chromosomes. A crucial part of meiosis occurs when both strands of DNA break in the same place and then are repaired by a process called recombination. But when there are too many double –strand breaks, they may not be repaired properly, leading to potentially mutations that can be transmitted to the offspring. methods The Sloan Kettering Institute (SKI) researchers used a strain of mutant mice as a means to uncover new clues about the process of meiosis, which forms eggs and sperm. They focused on male mice that were missing a gene called ATM. Mutations in ATM are associated with cancer, because they prevent cells from being able to recognize that they have damaged DNA, allowing many more mutations to accumulate. methods MEIOSIS (Normal) MEIOSIS Male Mice (missing ATM gene) About 300 of double-strand breaks in the DNA More than 10 times more double-strand breaks in their DNA Repaired by recombination properly Repaired by recombination less accurate discussion o Mice with no ATM had germ cells with more than 10 times more double strand breaks in their DNA, compared with what would occur during normal meiosis. o Double-strand breaks that happen in DNA usually repaired by homologous recombination, a process that occurs when the damaged DNA finds the matching genetic sequence and brings the two sequences together. This helps in dividing the chromosomes’ content. results By studying this process in mice with genetic defect leading to abnormally high DNA breaks in meiosis, the investigators were able to learn more about the consequences of these extra breaks. About 300 of these double-strand breaks occur during the normal formation of egg and sperm cells, but in mice with no ATM had germ cells with more than 10 times more double strand breaks in their DNA, compared with what would occur during normal meiosis. 3. T-cells could be made into better cancer killers by increasing their protein production By: Jessica E. Thaxton, Ph. D introduction • A team of scientists from Hollings Cancer Center at the Medical University of South Carolina (MUSC) has developed a novel flow cytometry technique that can, for the first time, quantify protein production in T-cells. • T cells are immune cells that surveil the body and can effectively target and kill cancer cells. However, when T cells are in the vicinity of a tumor, cancer cells sap their energy, leading to a decrease in their protein production. This change leads to T cells losing their tumor-killing ability. methods In the past four years, the team observed more than 50 human tumors, and in most tumors, they noticed the existence of T cells that made very little protein. To understand more fully about protein production in T cells in tumors, the scientists used two different types of signaling(cytokines) called IL-15 and IL-2. methods T Cells T Cells IL-15 IL- 2 Increase of protein production Controlled tumor growth Decrease of protein production Uncontrolled tumor growth discussion o The new technique, developed by the MUSC team, can be used to monitor protein production in T cells and understand how it becomes depressed in the tumor microenvironment. This paper establishes that T cells that are able to make protein in tumors have phenomenal ability to control tumor growth. o Since the team observed many tumors have T cells that made very little protein, this finding led them to surmise that there are T cells unable to make proteins residing in tumors. According to Thaxton, the new technology will help them to monitor these T cells and reawaken their protein production machinery and cancer-fighting ability. results The team found that T cells conditioned with IL-15 were able to make proteins in the tumor microenvironment and in tumors, whereas IL-2 conditioned T cells experienced diminished protein production in tumors. These results help scientists to understand how they can reawaken tumor T-cells and increase their protein production, thereby enhancing their ability to control tumor growth. results Thaxton believes that a simple strategy of combining modulator that changes the way that cells generate energy will allow T cells to experience sustained protein production in tumors and produce more effective immunotherapy treatments for patients. Unlike many, current immunotherapies, which can be quite expensive, this approach would be cost-effective and thus a more realistic strategy for treating cancer patients from all walks of life. Thaxton believes that the current study is the very first set of experiments that begin to describe the role of protein production in anti-tumor immunity. References http://www.sciencedaily.com http://www.new-medical.net http://www.eukalert.org Thank you!
