?A simple method for determining the target genes of transcription factors
By timothy auyeung, Section Biology Posted on Mon May 3rd, 2010 at 12:12:19 AM PST
In response to changes in physiological conditions, cells turn on and off the expression of specific groups of genes to initiate specific biological processes. The expression of these genes is controlled by the binding of transcription factors to short DNA segments called transcription factor binding sites (TFBS) located in the cis-regulatory regions of the genes (Stormo 2000). The bound transcription factors subsequently recruit RNA polymerase and other transcriptional machineries to synthesize gene transcripts. Together, these molecular players constitute the gene regulatory network that controls the expression of each gene in the cell. Obtaining a comprehensive understanding of the regulatory network will drive advancement in many fields including cancer and pathology research as the network allows the identification of novel drug targets. (710 words in story) More >>

?Genome methylation and folate intake
By daniellebourque, Section Biology Posted on Sun May 2nd, 2010 at 05:09:33 PM PST
The goal of this study is to view the effects of different diets on the methylation patterns of repetitive DNA sequences in mice. (4 comments, 161 words in story) More >>

?Alternative Splicing QTL
By gbaute, Section Biology Posted on Fri Apr 30th, 2010 at 11:54:02 PM PST
Alternative splicing (AS) is a essential form of gene regulation effecting up to 95% of genes in some eukaryotes, key players in its control are poorly understood. A large component of this unknown is the contribution of cis (signals on the RNA) and trans (mostly protein machinery) regulation. This experiment would identify the contribution of both as well as which regions in the genome are responsible. This experimental layout could be used for any species with AS but I think drosophila, which has very prevalent AS would be a good choice. Two divergent strains with different AS patterns will be crossed and then back-crossed to make a QTL population. Illuminia runs for each line (depending on funding could be 25-250 lines) will essentially do both parts of the experiment at once, it will assess transcriptome wide AS patterns and find (by allele specific snps) the contribution of each parent to the genome. QTL analysis will reveal which AS events are associated with which genomic regions. This is very similar to eQTL experiments. If most AS events are associated with the loci that the genes come from then cis control is important for that allele if its from another region then its trans. This would further our understanding of AS and possibly reveal new mechanisms of its control. A bonus will be assessing how AS may have diverged in these species. (6 comments) Comments >>

?Alternate Interactomes
By xerro five, Section Biology Posted on Fri Apr 30th, 2010 at 11:39:26 PM PST
Based on the recent publication, The Genetic Landscape of a Cell, and other similar studies, a lot of information is currently known about the basic "wiring" of molecular pathways leading to cellular function. Interaction maps such as the one produced for yeast by this paper are great descriptions of how a cell lives in controlled laboratory environments, but relatively less is known about compensatory pathways that could arise as a result of environmental change. It will be possible to take advantage of the existing data on standardized condition pathways as a control so as to discover any new interactions that become active in a modified environment. In light of this publication creating the most detailed interaction map for any organism to date, and the relative ease of use, let's begin with manipulation of yeast cells for this experiment. This type of analysis is something that Costanzo et al hint at a few times in their paper. (1 comment, 680 words in story) More >>

?Indirect targeting of an elevated GTPase in ovarian cancer
By Aina, Section Biology Posted on Fri Apr 30th, 2010 at 10:36:01 PM PST
Ovarian cancer is the leading cause of cancer death among gynecological malignancies, and it ranks as the fifth most frequent cause of cancer death in women. Elevated expression of Rab25 has been associated with ovarian cancer pathogenesis. Rab proteins are Ras-like small GTPases that are activated and deactivated dependent on their GTP- and GDP-bound form. The conversion between the two forms is orchestrated by various factors, including GDF (GDI displacement factor). Identification of the Rab25 associated GDF could provide a target for inhibition of growth of human epithelial ovarian cancer cells. So I propose an experiment to examine all protein-protein interactions that involves Rab25 in order to identify the Rab25 associated GDF. Other Rab associated GDF have already been identified, and their sequence will be used in order to look for sequence homolgy in our protein-protein interaction hits (yeast two-hybrid screen). Candidate Rab25 associated GDF will be tested for function in a nucleotide exchange assay, to confirm that they actually function as a GDF and enable the release of GDP-bound Rab25 so that it is in its free form where it is able to convert to active GTP-bound Rab25.   The next step will then be to target this Rab25 associated GDF through RNAi in order to knock it down. One can study the effect this will have on inhibiting tumor growth in human epithelial ovarian cancer cells by applying it on ovarian cancer cell lines. Hopefully this will lead to an inhibition of tumor growth, and one will have managed to identify a novel form of approach to ovarian cancer therapy that might improve patient management. Stenmark, H. (2009) Rab GTPases as coordinators of vesicle traffic. Nature Reviews, Molecular Cell Biology, 10; 513-523. Cheng, K.W., Lahad, J.P., Kuo, W., Lapuk, A., Yamada, K., Auersperg, N., Liu, J., Smith-McCune, K., Lu, K.H., Fishman, D., Gray, J.W., and Mills, G.B. (2004) The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers, Nature Medicine, 10,11; 1251-1256. Dirac-Svejstrup, A.B., Sumizawa, T., and Pfeffer, S.R. (1997) Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI. The EMBO Journal, 16, 3; 465-472. (4 comments) Comments >>

?Systems Biology Approach to Identifying Biomarkers for Predict Sensitivity to Cancer Drugs
By Kendric, Section Biology Posted on Fri Apr 30th, 2010 at 09:44:25 PM PST
Background Although heterogeneity between tumours of the same cancer type can affect its sensitivity to drug treatments, we still typically treat patients with the same series of drugs. Alternatively, we should aim to tailor specific treatments to individual patients based on the tumour's profile. For this goal, I propose using a systems biology approach integrating genomic, transcriptomic, and proteomic data to identify biomarkers that can predict a tumour's sensitivity to cancer drug. (1 comment, 304 words in story) More >>

?Epigenome association study
By shengliu, Section Biology Posted on Fri Apr 30th, 2010 at 04:15:43 PM PST
In the process of disease initiation, there are bunch of genes been inactivated through epigenetic approach, such as DNA methylation or histone modification. The example include MLH1 methylaiton in colorectal cancer. This idea is to find genes inactivated in the epigenome through populations, The approach is the same as normal Genome wide association study (GWAS), the difference is the target. Detail: Get patient sample and normal sample from some tissue, like colon. Get DNAs from the sample and treat with bisulfite. Bisulfite chip (if there is*) analysis of the data from patient and normal. *  Bisulfite Chip, (maybe also a new idea:). the company should make this product, their CpG island Chip is not accurate enough to locate genes. and it is doable as what they need to do is just bisulfite convert the sequence they usually attach to the chip) (5 comments) Comments >>

?iPS cells for the study of dyskeratosis congenita
By SarahLepage, Section Biology Posted on Fri Apr 30th, 2010 at 04:15:18 PM PST
Dyskeratosis congenita (DC) is a very rare congenital disorder that is characterized by symptoms that resemble premature aging.  DC is a disorder of defective telomere maintenance, related to mutations in the vertebrate telomerase RNA component (TERC).A recent paper by Agarwal et al. successfully generated induced pluripotent stem (iPS) cells from DC patients, renewing their telomerase function.  I propose an experiment to study at what point the DC iPS cells lose their renewed telomerase function by inducing these DC iPS cells to differentiate and monitoring their TERC expression over time as compared to normal iPS cells. (5 comments, 505 words in story) More >>

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