Flt3-KO Mice Case Study

The CFTR gene encodes a protein that is present in epithelial tissues in lungs, sweat glands, and pancreas, and helps

A lymphoid progenitor will begin to develop into a T-cell if the Notch1 protein is overexpressed in the cell. During the double negative 1 (DN) phase of development, the cells are migrating into the thymic cortex as pro-thymocytes from the bone marrow. They are yet to commit to a lineage so can still mature into other types of T-cell such as natural killer T-cells, intraepithelial lymphocytes and regulatory T-cells. Also, the cells are yet to express CD4+ or CD8+ and only express c-kit (CD117) and CD25 on their cell membrane.

DeltaF508 is the most common mutation, accounting for about 70% of CF chromosomes worldwide. However, over 1,500 mutations have been reported. These mutations cause there to be little to no functional CFTR to be produced.

Another health problem that treatment with embryonic stem cells can cause is tissue rejection. As is the case with current organ transplantation procedures, embryonic stem cells are harvested from many people all who possess a unique set of genes; therefore, the stem cells are not genetically matched for each patient (Herold 48-49). The difference in genetics causes the body to reject the tissue and the immune system begins to attack the transplanted tissue like it would a virus or bacteria in an attempt to remove the perceived threat. To avoid the implanted tissues being rejected by the body, doctors must prescribe immune suppression drugs that must be taken for the remainder of the patient’s life, even with these drugs the tissue may still be rejected and

Frank Emmrich is the director of the Fraunhofer IZI and a professor at the University of Leipzig, where he has headed the Institute of Clinical Immunology and Transfusion Medicine since 1994. This dual position enables the efficient sharing of experience, not to mention the optimal supervision of undergraduate and doctoral dissertations, and provides an excellent basis for cooperation. Both a doctor and an immunologist, Prof. Emmrich spent 13 years as both a researcher and department head at Max Planck Institutes in Freiburg and Erlangen. Over seven of these years he was a professor at the Friedrich Alexander University in Erlangen-Nuremberg. From its founding eight years ago up to this year he also was director of the BMBF funded institute of Translational Regenerative Medicine, the TRM, at Leipzig. Since 2008 he is also a member of the German Ethics Council and additionally member or chairman in a multitude of scientific organisations such as the German Stem Cell Network. He first came into contact with Dr. Burkhardt during her dissertation thesis on genetics of autoimmune diseases and since 2011 advised and accompanied Dr. Burkhardt’s BMBF funded project as her mentor at the Translational Center for Regenerative Medicine (TRM) Leipzig. Currently, more than 200 peer-reviewed scientific publications are listed by Prof. Emmrich in addition to several patent applications. In addition to supervision provided by Prof. Emmrich, Christopher Oelkrug, Head of Immunotherapy/Oncology Unit at the Fraunhofer IZI, will accompany the proposed project. He published over 20 peer-reviewed research articles with a focus on the development and testing of novel therapeutic strategies with the aid of innovative tumour models for the treatment of cancer patients and the enhancement of therapeutic cancer vaccines through different administration strategies. Thus, his research and expertise complements the purposed of this

all cases of FXS are developed through the mutation in the FMR1 gene where a part of the DNA (known as CGG triplet repeat) is expanded

The gene can be alternative spliced in exons 12, 14, 15 and 17 resulting in different mRNAs and protein isoforms. The CGG trinucleotide repeat in the non-coding part of the FMR1 gene is unstable, thus the repeat length varies among normal population, with normal individuals ranging from 6-55 repeats. The trinucleotide repeat often becomes unstable during maternal transmission to the next generation, giving rise to the expansion of the repeat. Individuals with 55-200 CGG repeats are considered premutation carriers, and in patients with FXS the CGG repeats are above 200 resulting in hypermethylation and therefore silencing of the gene’s CpG site in the promoter region (Willemsen R., 2011). Pietrobono and her team, studied the events prior to the inactivation of the FMR1 gene and demonstrated that the initial events seem to be histone deacetylation and H3-K9 methylation, followed by DNA methylation and H3-K4 demethylation (Pietrobono, R., Tabolacci, E., Zalfa, F., 2005). However, work carried out on human embryonic stem cells has proven that FMR1 inactivation is a result of downregulation of transcription and chromatin modifications, prior to DNA methylation (Willemsen R.,

Graft rejection: Type IV hypersensitivity. Type IV hypersensitivity is a delayed hypersensitivity as the reaction takes more than 12 hours. It is mediated by T helper cells and cytotoxic T cells and does not involved antibodies. In graft rejection, the rejection is caused by foreign MHC antigens as the T cells responds to them by attacking the foreign MHC antigens when they are being recognized. Rejection also only takes place after a few hours to months and years depending on the type of

The Fc receptor is a receptor for the Fc portion of immunoglobulins. This receptor is found on the surface of mainly immune cells. They have a protective function and bind to antibodies attached to infected cells or invading pathogens. They can stimulate phagocytotic or cytotoxic cells. Fc receptor polymorphisms FcIIIA-V158F and FcIIA-H131R are significantly associated with lower body surface area (BSA) of psoriasiform plaques in the intermediate point of treatment with TNF-alpha inhibitors (P=0.02, P=0.03) (Julia, M).

The CFTR protein is a channel protein which is responsible for controlling the movement of water and halogens from inside to outside of the cell. When the CFTR protein does not work, chloride and thiocyanate are trapped inside the cells in the airway and outside in the skin. So these ions cannot flow out of the cell due to a blocked channel. This causes cystic fibrosis, characterized by the build-up of thick mucus in the lungs.

Many experiments on mice have been done with success, however very few experiments have been done on humans. This means that there still needs to be some more research and clinical trials done before it is used as a treatment option but the promise of this therapy emerging is high. In a recent study done in 2013 by Issa, human Treg cells have been proven to prevent human graft rejection. This study was done by implanting human skin tissue onto a mouse that lacked Rag and therefore was immunocompromised and did not have its own immune T-cells. The mouse was then infused with human blood cells that either had no expansion of Treg cells or had extensive expansion of Treg cells. The mice that received the human blood with the extensive expansion of Treg cells were able to maintain the health of the transplanted human skin graft. The mice that received the blood without the expanded Treg cells were not able to keep the tissue healthy and went through the rejection process4. This study is important in proving that human Treg cells have the ability to prevent rejection without the need of immunosuppressant

One of the less common mutation of patients with Cystic Fibrosis causes a substitution of glycine for aspartic acid at amino acid 551 (G551D-CFTR); this mutation occurs in approximately 4% to 5% of persons with cystic fibrosis. Agents that increase the ion-channel function of activated cell-surface CFTR are referred to as “potentiators.” VX-770 is an investigational, orally bioavailable CFTR potentiator that has been shown to increase the activity of wild-type and defective cell-surface CFTR protein in vitro. The greatest effect of VX-770 was on cells with G551D-CFTR.the following investigation was executed in two parts: Part 1; 20 patients were assigned to receive VX-770 every 12 hours with doses of 25, 75 or 150mg or placebo followed by

BiFC is a technique to test for interactions between two proteins by fusing different fluorescent fragments to the two putative partners. If the proteins in fact bind, fluorescence will be observed as the two fragments are brought into close proximity. Yolk platelets make Xenopus cells highly autofluorescent, so we will use a variant of enhanced yellow fluorescent protein (EYFP) called VENUS that matures more rapidly than EYFP and is more resistant to pH. We will cleave VENUS at position N144 as used in previous Xenopus BiFC experiments29,30. We will amplify each fragment by PCR and clone into the expression vector pCS2+. We will then fuse one of these fragments to the N-terminus of FMRP and the other fragment to the 5’ end of Cyclin E mRNA, amplify our constructs by PCR, and check the constructs by sequencing. We will

The disorders have been getting more and more complex and the variables within the phenotypes have been even more difficult to figure out as the times go on. Dr. Jonathan Flint states that there is not a simple answer for this general question, and states that “there is variation in genetic architecture among phenotypes.” One research shows that twenty-two CF patients had similar mutations and compound heterozygotes. From this study, we can clearly see how the phenotypes and tracing it back to connect it with

In addition to the hybrid phenotypes co-expressing two lineage specifying T cells, we also obtained phenotypes with the activity of more than two TFs, i.e., Th1-Th2-Treg, Th1-Th17-treg, and Th1-Th2-Th17-Treg. It was shown previously that the basal levels of Tbet and GATA3 can be expressed by subset of Treg cells and the dynamic balance of these TFs helps in maintaining immune tolerance (Yu et al., 2015). Here, we predict the novel phenotypes that can activate three TFs (Tbet-GATA3-Foxp3, Tbet-RORγt-Foxp3) and all four TFs (Tbet-GATA3-RORγt-Foxp3). However, in these phenotypes Tbet and GATA3 have the higher activity levels than the activity levels of Foxp3.