মলিকুলার প্রকল্প

মলিকিউলার বায়োটেকনোলজি বিভাগের চলমান প্রকল্প

1. Investigations of genes and genetic variants in order to assess their association with diseases in Bangladeshi population

1.1 Single nucleotide Polymorphism (SNP) study on HMG-CoA in Bangladeshi Population

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration: 2018-Present

Details:

In humans, HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase/HMGCR) is 888 amino acids long transmembrane protein containing two domains. HMGCR gene is located on the long arm of the fifth chromosome: 5q13.3-q14 and is composed of 19 exons. In the Mevalonate pathway, it catalyzes the conversion of HMG-CoA to Mevalonic acid, the key regulatory step in cholesterol biosynthesis.

In Bangladesh, CVD ranked fifth in causing death comprising 17% of total mortality. Multiple genes and complex genetic dysregulation are responsible for CVD. SNPs are potential candidates for causing CVD. SNPs also interfere with drug efficacy and doses in the treatment of CVD. Thus, susceptible SNPs pinpointing is essential to understand the basis of genetic aberration associated with a disease in a specific population. Therefore to find out the frequency of SNPs on the HMGCoA reductase gene and their association with CVD and to explore CVD drug-SNPs interaction in the Bangladeshi population are of immense importance. Elucidating the association of dose-response of specific drugs i.e. Statin with particular SNPs will help to determine suitable drug and dose regimens for Bangladeshi CVD patients due to polymorphism. This study will lead to novel biomarker development for the precise diagnosis of CVD. Also, evolutionary pattern forcing nucleotide variation as well as genetic mapping could be carried out using this gene polymorphism data. Briefly, this study will add a new dimension for cardiovascular disease management in Bangladesh.

2. Investigation of disease-associated genes and genetic variants as well as identification of disease biomarkers

2.1 Association of type 2 Diabetes linked genetic variants to gestational diabetes mellitus in the Bangladeshi women

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration: 2016-Present

Details: Gestational diabetes mellitus (GDM) is a major public health problem because of its prevalence and its associated complications during pregnancy. It is a complex metabolic disorder of pregnancy that is suspected to have strong genetic predisposition. Both GDM women and their offspring are at increased risk of future development of type 2 diabetes mellitus (T2DM). Prevalence of GDM is very high in Bangladeshi women like other countries in Asia especially south Asia. In most of the cases GDM patients get temporary relief from diabetes post-partum and are unaware of the fact of being diabetic in later life. Therefore, a systematic study to find out whether GDM and T2DM share a common genetic background in our population is crucial to prepare GDM patients for future encounter of T2DM.

2.2 Expression analysis of KLHDC10, PLEKHD1, ZSWIM5, LRRC3B AP006621.6, RP11-218M22.1. RP11-467J12.4 and CTD-3032H12.1 genes in breast cancer patient

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration: 2021-Present

Details:

2.3 Association between oxidative stress and telomere length in type 2 diabetes

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration: 2022-Present

Details: Oxidative stress is a component of several diseases including cardio-vascular diseases (CVDs), chronic obstructive pulmonary disease (COPD), chronic kidney disease and neurodegenerative disease. It is also involved in the development of diabetes and its associated vascular complications. Likewise, telomere length may be implicated in multiple diseases such as cancer, type 2 diabetes (T2D) and cardiovascular diseases. In fact, a meta-analysis revealed a significant association between shortened telomere length and T2D. Telomere shortening has been identified as a risk factor for T2D, and a number of studies have elucidated correlation between telomere attrition and insulin resistance, impaired glucose tolerance, obesity and inflammation. In addition, variants in telomere maintenance genes may be associated with the pathogenesis of T2D. Furthermore, a longitudinal study of a Chinese population group suggested that leukocyte telomere length, which can be measured as a marker of overall telomere length, may be an independent predictor of T2D risk and telomere erosion might participate in T2D pathogenesis independently of conventional T2D risk factors, mitochondrial DNA copy number, oxidative stress and inflammation. Although oxidative stress and telomere shortening have been shown to be associated with T2D, the relationship between these two factors is yet to be clarified as there are conflicts between the findings of experimental studies and those of correlative studies in this regard. Therefore, it is crucial to determine the correlation between oxidative stress and telomere length in T2D patients in order to better understand the development and progress of this metabolic disease. It should also be noted that the levels of several oxidative stress markers including, but not limited to, malondialdehyde, advanced oxidation protein products, catalase, superoxide dismutase, reduced glutathione and protein carbonyls may be altered in T2D. Additionally, levels of plasma antioxidants such as uric acid and albumin may be related to oxidative stress, with possible implications in T2D. If these oxidative stress markers can be correlated with telomere length, measuring these markers can provide valuable information regarding cellular health. Altered expression levels of some genes may impact telomere length. For example, down regulation of sirtuin 1 (SIRT1), which takes part in telomere end protection and glucose metabolism, has been implicated with shortened telomere in diabetic rodents. Thus, evaluation expression level of such genes may provide deeper insights into the mechanism of telomere shortening in T2D.

3. Pharmacogenetics and Pharmacogenomics

3.1 Pharmacogenomics (PGx) study of antipsychotic drugs in Schizophrenic patients

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration:

Details:

4. Improving agronomic traits of food crops using CRISPR/Cas-mediated genome editing technology along with gene cloning and characterization techniques

4.1 Editing multiple isoforms of starch branching enzymes in rice through multiplex CRISPR/Cas9 to generate diabetes friendly high-amylose containing rice

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration:

Details:

5. Isolation and characterization of novel antidiabetic compounds

5.1 Identification and characterization of economically valuable flora as well as appraisal of their antidiabetic properties of the hill tracts of Bangladesh

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration: December, 2019-Present

Details:

Most people depend on flatland for the food source. To reduce this pressure and to make the diverse source of food we can look for alternative source e.g., alpine resources. Moreover, a huge portion of people is not habituated with alpine flora which can be a great source of nutrition and. At the same time, these indigenous floras are reported to have medicinal value. On the other hand, metabolic disease like dyslipidemia and diabetes constitutes a major emerging health crisis in the world. Diabetes remains an incurable disease and has become the third major cause of death after cancer, cerebrovascular and cardiovascular diseases. Despite insulin therapy and the availability of different synthetic analogs, the world's diabetic population is expected to show a steady growth of 366 million by 2030. It is known that a diet rich in indigenous products is considered to result in a lower incidence of diabetes, cancer, and obesity. Moreover, some species of mangroves have been used for a long time as a remedy for diabetes in folk medicine. Considering all these issues the present proposal has been premeditated. Alpine species include microflora (bacteria, actinobacteria, cyanobacteria, and fungi), microalgae, macroalgae (seaweeds), marine phytoplanktons, and flowering plants and other halophytes. The pharmacological functions of alpine natural products to develop new potent drugs including anticancer, anti-diabetic, anti-human immunodeficiency virus, Alzheimer's and many other disease therapeutics are of importance now a days. The past was considered the synthetic era due to the commercial production of synthetic drugs by the pharmaceutical industry. Continuous use of synthetic drugs causes severe side effects and led to the resistance of microbes. Also, synthetic drugs are expensive and large populations cannot afford to get benefits from these drugs. So, a global trend with a focus on green medicines due to minimum side effects and cost-effectiveness is increasing. Medicinal plants play an appreciable role in the development of modern herbal medicines. The bioactive compounds of medicinal plants are used as antidiabetic, chemotherapeutic, antiinflammatory, antiarthritic agents where no satisfactory cure is present in modern medicines. In recent years herbal medicines have started to gain importance as a source of hypoglycemic agents. It is estimated that more than a thousand plant species are being used as a folk medicine for diabetes. The objectives of this study are 1. To collect and locally identify important flora with medicinal properties from Chittagong hill tracks; 2. To store genomic DNA and molecular identification of collected flora; 3. To prepare herbarium and plant medicinal flora; and 4. To screen and evaluate the flora for putative antidiabetic activity.

6. Molecular diagnosis of diseases

6.1 Fabrication of biosensor based on nanostructured based materials

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration:

Details:

7. 4^th Industrial Revolution (4IR)-related project

7.1 Production of bacteriophage-encoded proteins and assessment of their utility as potent antimicrobial agents against urinary tract infection (UTI) and skin infection

Funding: National Institute of Biotechnology

Implementation: Molecular Biotechnology Division

Duration: 2022 - Present

Details: The arbitrary use of antibiotics has expedited the emergence of antimicrobial resistance (AMR). Especially, multidrug resistant (MDR) pathogens have become a major health crisis all around the globe. In this so-called “post-antibiotic” era, infections with MDR and extreme drug resistant (XDR) bacterial pathogens are causing a significant rise in patient death. The use of bacteriophages or phages, which is termed phage therapy, can be a rescuer in this context. This approach has several advantages over chemical antibiotic agents, and its major advantages include high specificity, self-dosing, low inherent toxicity, narrower potential for inducing resistance, low cross-resistance with antibiotics, application versatility and biofilm clearance among others. To treat bacterial infections, phages can be utilized in three different ways- i) synthetic phage engineering, ii) phage protein engineering and iii) phage-inspired antibacterial designing. It is well-known that that a number of enzymes (e.g., endolysin) can show antibacterial properties, and these enzyme-based antibacterials are known as enzybiotics. In addition, phage coat proteins can also have antibacterial properties. In the present study, we intend to investigate the antimicrobial effects of phage-derived especially endolysin and coat protein against a number of bacterial pathogens causing urinary tract infection and skin infection.