Biotechnology and Genetic Engineering

Abdulla Al Noman

Research Assistant, International Centre for Diarhoreal Disease Research, Bangladesh.

Thesis Title: A System Biology Approach to Investigating Significant Biomarker, and Drug Target Common Among Patients with Gonorrhea, Chlamydia and Prostate Cancer: A Pilot Study

Overview: Having a previous history of sexually transmitted diseases (STDs) such as gonorrhea and chlamydia increases the chance of developing prostate cancer, the second most frequent malignant cancer among men. However, the molecular functions that cause the development of prostate cancer in persons with gonorrhea and chlamydia are yet unknown. In this study, we studied RNA-seq gene expression profiles using computational biology methods to find out potential biomarkers that could help us in understanding the patho-biological mechanisms of gonorrhea, chlamydia, and prostate cancer. Using statistical methods on the Gene Expression Omnibus (GEO) data sets, it was found that a total of 22 distinct differentially expressed genes were shared among these 3 diseases of which 14 were up-regulated (PGRMC1, TSC22D1, SH3BGRL, NNT, CTSC, FRMD3, CCR2, FAM210B, VCL, PTGS1, SLFN11, SLC40A1, PROS1, and DSE) and the remaining 8 genes were down-regulated (PRNP, HINT3, MARCKSL1, TMED10, SH3KBP1, ENSA, DERL1, and KMT2B). Investigation on these 22 unique dysregulated genes using Gene Ontology, BioCarta, KEGG, and Reactome revealed multiple altered molecular pathways, including regulation of amyloid precursor protein catabolic process, ferroptosis, effects on gene expression of Homo sapiens PPAR pathway, and innate immune system R-HSA-168249. Four significant hub proteins namely VCL, SH3KBP1, PRNP, and PGRMC1 were revealed by protein-protein interaction network analysis. By analyzing gene-transcription factors and gene-miRNAs interactions, significant transcription factors (POU2F2, POU2F1, GATA6, and HIVEP1) and posttranscriptional regulator microRNAs (hsa-miR-7-5p) were also identified. Three potential therapeutic compounds namely INCB3284, CCX915, and MLN-1202 were found to interact with up-regulated protein C-C chemokine receptor type 2 (CCR2) in protein-drug interaction analysis. The proposed biomarkers and therapeutic potential molecules could be investigated for potential pharmacological targets and activity in the fight against in patients with gonorrhea, chlamydia, and prostate cancer.

Tasmiah Feroz

Thesis Title: Predicting the damaging impact of nsSNPs on Human tumor suppressor CYLD gene: A Comprehensive Insilico study

Overview: Cylindromatosis protein (CYLD) known as a potent tumor suppressor regulates NF-kB and JNK signaling pathway by cleaving K63 linked poly-ubiquitin chain from its substrate molecules and thus prevent the progression of tumorigenesis and metastasis of the cancer cells. Mutations in CYLD can cause aberrant structure and abnormal functionality lead to the tumor formation. In this present study, we utilized several computational approaches such as PANTHER, PROVEAN, PREDICT SNP, POLYPHEN 2, PHD SNP, PON P2, SIFT to find out deleterious nsSNPs. We also highlighted the damaging impact of those deleterious nsSNPs on the structure and function of the CYLD utilizing Consurf, I-Mutant, SDM, Phyre2, HOPE, Swiss PDB Viewer, Mutation 3D.We shortlisted 18 highly risk nsSNPs from total 446 nsSNPs recorded in NCBI database. Based on conservation profile, stability status, structural impact analysis we finalized 13nsSNPs. Molecular docking analysis and molecular dynamic simulation concluded the study with the findings of two significant nsSNPs: R830K, H827R having remarkable impact on binding affinity ,RMSD, RMSF, Radius of gyration and hydrogen bond formation during CYLD-ubiquitin interaction. Principal component analysis provided comparison between native and two mutant variant of CYLD that signifies structural and energy profile fluctuations during MD simulation. Protein-protein interaction network constructed to analyze the functional interaction pattern of CYLD with 20 proteins involved in several biological pathways that can be impaired by mutant variants. Considering all these insilico analysis, our study recommended cancer associated functional SNPs which will be particularly important for conducting large-scale studies as well as designing precision medications against diseases associated with these polymorphisms.