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Note: Challenges with biomarkers in cancer drug discovery and development (doi:10.1080/17460441.2018.1479740) Precision medicine; 1. require molecular profiles of tumors 2. require molecular profiles of microenvironment 3. individual features Final aim is to use these data to cure the cancer patient effectively! However, the authors mentioned that it only partially helps. Also, the patients who have a good response, at the very end, they develop the resistance to the treatment, either targeted molecule or immunotherapy. Gap; Need to identify the biomarkers in each step of cancer progression as well as the treatment effectiveness (resistance or sensitivity). Cancer biomarkers -- tumor characteristic or response of the body in the presence of cancer which can be measured and evaluated (can be directly from the cancer or the response from the host body). Definition of each biomarkers; 1. diagnostic markers - predisposition and early detection of tumors in healthy patient

Note: Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy (doi: 10.1016/j.chembiol.2017.08.027) Process that maintain genome integrity in normal cells - it will help cancer to develop resistance to radiation and DNA-damaging chemotherapeutics. New target; RAD51 recombinase, RAD52, and MRE11 nuclease, WRN DNA helicase. Synthetic lethality - two individual mutations but when combined  resulting in lethal phenotype. Hartwell, is the first guy who initiated the synthetic lethality with the cancer baring the DNA-repair proteins defect. Also, cancer that addict to particular DNA repair mechanism. Therefore, the target for synthetic lethality is that finding the protein that the cancer cell relied on for viability (but less important in normal cell) and inhibit theirs function. Synthetic lethality; two types 1.between-pathway (each backup for each other) 2.In-pw synthetic lethality, mutation either way of reversible step --&g

It is good to visit the IMB website, time to time. It has been changed a lot since I graduated from there. I think these two articles are very useful for both academic, academic supporting staff as well as the students. 1.Writing a research paper: A practical guide for students http://www.mb.mahidol.ac.th/e-doc-se/uploads/5b6918fb5d38b.pdf Suggested ways to write; 1.Present the story 2.Start with figure and table 3.Materials and Method 4.Results 5.Discussion 6.Introduction 7.Abstract 8.Title 2.Knowledge management report:  Papers and publishing http://www.mb.mahidol.ac.th/e-doc-se/uploads/5a7801aa2faf0.pdf Suggested management; 1.the raw data should be kept for at least 7 years 2.criteria for giving the authorship in the medical journal;  http://www.icmje.org/ I have heard the criteria several times since I was a MS-post-graduate student, even debating in the small lab meetings in the US or here Thailand. 3.For the suggested reviewers (it can be applied to my cu

My ABC to Protein post-modification in higher Eukaryote! 1.Phosphorylation 2.Ubiquitination 3.Acetylation 4.Methylation 5.SUMO 6.Glycosylation 7.S-nitrosylation 8.Lipidation 9.Proteolytic cleavage 10.PARylation 11.Neddylation 12.Malonylation 13.Propionylation 14.Crotonylation 15.Citrullination 16.Carbonylation 17.ADP ribosylation 18.Hydroxylation 19.Iodination 20.Addition of prosthetic group 21.Isopeptide bond Anything else? -- and yes there is ...... It sounds to me those PTMs reflect the microenvironment within the cell, as a result, it regulates the cellular function and response. The paper basically focuses on the epigenome (mostly histone and DNA). It is a very nice piece of illustration. doi:  10.1080/17460441.2017.1295954 Exploring the epigenetic drug discovery landscape ---

Note for: Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair-deficient chicken DT40 cell lines (doi: 10.1002/em.20656) US Tox21 program -- evaluate the detection of genotoxic cpds. This study focused on cytotoxicity by using DT40 with deficient in DNA repair pathway. Using 7-isogenic DNA repair-deficient pw cell line to identify the types of DNA damage. Criteria to judge; 1.clastogenicity (ability to break the DNA) in mutant and WT 2.ability to induce gH2Ax positive foci by melphalan 3.72-hr viability through the liquid assay 4.using more DNA repair deficient cell lines to clearly identify the damage induced 5.involvement of ROS in induction of DNA damage At the end, it proposed that DT40 and theirs DNA-repaired deficient lines are useful tool to detect 1.genotoxic cmp. 2.identify the nature of DNA damage of the challenges 3.analyzing mechanism of mutagenesis Rational; Because of the number of chemica

Note: RAD18 and Poly(ADP-Ribose) Polymerase Independently Suppress the Access of Nonhomologous End Joining to Double-Strand Breaks and Facilitate Homologous Recombination-Mediated Repair (doi: 10.1128/mcb.01243-06) Rad18 in yeast involves in post-replication repair but not dsb repair. Show less sensitivity toward cpt when generating ko. In contrast, Rad18 ko in dt40 showed high sensitivity toward cpt and involve in hr to repair dsb. The authors mentioned that when deleting another key factor of nhej in hr deficient cell, and thus restoring the activity of hr, this mean that that hr factor (Rad18) plays role in the balancing between hr and nhej. At stalled replication fork, Rad18 and Parp1 are used to control the balance between hr and nhej, by which the suppress the nhej to prevent toxic nhej during replication folk collapse. PRR - there are two pws, 1.translesion, 2.template switch via HR Translesion using the specialized polymerase to bypass the damage. Rad6 and Rad18

A brief overview of how to get the 3D protein structure. 1. gene of interest 2. cloning it 3. expressing it 4. purify it 5. crystallize it - not really depend on protein size, it is the matter of luck, patient, and good observations. Three methods; microbatch -- good for screening (sample and precipitant are mixed and covered by the paraffin oil), vapor diffusion -- hanging drop (using the exchange between precipitant and reservoir), liquid diffusion -- hard to implement To solve with Synchrotron - the crystal should be in the range between 20-200 micrometers. Way to differentiate the protein crystal from the salt; staining with Coomassie after running the SDS-PAGE or directly checking from the diffraction - salt and protein give a very different diffraction pattern. 6. X-ray diffraction--phase--electron density map obtain--fitting--building the model! 7. Analyze data 8. Submit the 3D information at PDB Protein crystallography really depends on luck and it is the fine pie