Biology subjects

Deshpande, S.

Publications and source records attributed to Deshpande, S..

3 recordsLinked to original sources

bioRxiv2019

An integrated microfluidic platform for quantifying drug permeation across biomimetic vesicle membranes

The low membrane permeability of candidate drug molecules is a major challenge in drug development and insufficient permeability is one reason for the failure of antibiotic treatment against bacteria. Quantifying drug transport across specific pathways in living systems is challenging since one typically lacks knowledge of the exact lipidome and proteome of the individual cells under investigation. Here, we quantify drug permeability across biomimetic liposome membranes, with comprehensive control over membrane composition. We integrate the microfluidic octanol-assisted liposome assembly platform with an optofluidic transport assay to create a complete microfluidic total analysis system for quantifying drug permeability. Our system enables us to form liposomes with charged lipids mimicking the negative charge of bacterial membranes at physiological salt and pH levels, which proved difficult with previous liposome formation techniques. Furthermore, the microfluidic technique yields an order of magnitude more liposomes per experiment than previous assays. We demonstrate the feasibility of the assay by determining the permeability coefficient of norfloxacin across biomimetic liposomes.

biophysics↗

bioRxiv2019

Microhomology-mediated end joining drives complex rearrangements and over expression of MYC and PVT1 in multiple myeloma

MYC is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. MYC is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that MYC rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1267). Rearrangements were complex and associated with increased expression of MYC and PVT1, but not other genes at 8q24. The highest effect on gene expression was detected in cases where the MYC locus is juxtaposed next to super-enhancers associated with genes such as IGH, IGK, IGL, TXNDC5/BMP6, FAM46C and FOXO3. We identified three hotspots of recombination at 8q24, one of which is enriched for IGH-MYC translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the IGH locus occur through non-homologous end joining, whereas secondary MYC rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates MYC rearrangements. Rearrangements resulted in over-expression of key genes and ChIP-seq identified that HK2, a member of the glucose metabolism pathway, is directly over-expressed through binding of MYC at its promoter.

cancer biology↗

bioRxiv2018

Genome-wide Population Structure Analyses of Three Minor Millets: Kodo Millet, Little Millet, and Proso Millet

Millets are a diverse group of small-seeded grains that are rich in nutrients but have received relatively little advanced plant breeding research. Millets are important to smallholder farmers in Africa and Asia because of their short growing season, good stress tolerance, and high nutritional content. To advance the study and use of these species, we present a genome-wide marker datasets and population structure analyses for three minor millets: kodo millet (Paspalum scrobiculatum), little millet (Panicum sumatrense), and proso millet (Panicum miliaceum). We generated genome-wide marker data sets for 190 accessions of each species with genotyping-by-sequencing (GBS). After filtering, we retained between 161 and 165 accessions of each species, with 3461, 2245, and 1882 single-nucleotide polymorphisms (SNPs) for kodo, proso, and little millet, respectively. Population genetic analysis revealed 7 putative subpopulations of kodo millet and 8 each of proso millet and little millet. To confirm the accuracy of this genetic data, we used public phenotype data on a subset of these accessions to estimate the heritability of various agronomically relevant phenotypes. Heritability values largely agree with the prior expectation for each phenotype, indicating that these SNPs provide an accurate genome-wide sample of genetic variation. These data represent one of first genome-wide population genetics analyses, and the most extensive, in these species and the first genomic analyses of any sort for little millet and kodo millet. These data will be a valuable resource for researchers and breeders trying to improve these crops for smallholder farmers.

genetics↗