Farzana Rahman

Highlights from the tenth ISCB Student Council Symposium 2014

This report summarizes the scientific content and activities of the annual symposium organized by the Student Council of the International Society for Computational Biology (ISCB), held in conjunction with the Intelligent Systems for Molecular Biology (ISMB) conference in Boston, USA, on July 11th, 2014.

Biochemical, Transcriptional, and Bioinformatic Analysis of Lipid Droplets from Seeds of Date Palm (Phoenix dactylifera L.) and Their Use as Potent Sequestration Agents against the Toxic Pollutant, 2,3,7,8-Tetrachlorinated Dibenzo-p-Dioxin

Contamination of aquatic environments with dioxins, the most toxic group of persistent organic pollutants (POPs), is a major ecological issue. Dioxins are highly lipophilic and bioaccumulate in fatty tissues of marine organisms used for seafood where they constitute a potential risk for human health. Lipid droplets (LDs) purified from date palm, Phoenix dactylifera, seeds were characterized and their capacity to extract dioxins from aquatic systems was assessed. The bioaffinity of date palm LDs toward 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins was determined. Fractioned LDs were spheroidal with mean diameters of 2.5 µm, enclosing an oil-rich core of 392.5 mg mL-1. Isolated LDs did not aggregate and/or coalesce unless placed in acidic media and were strongly associated with three major groups of polypeptides of relative mass 32–37, 20–24, and 16–18 kDa. These masses correspond to the LD-associated proteins, oleosins, caleosins, and steroleosins, respectively. Efficient partitioning of TCDD into LDs occurred with a coefficient of log KLB/w,TCDD = 7.528 ± 0.024; it was optimal at neutral pH and was dependent on the presence of the oil-rich core, but was independent of the presence of LD-associated proteins. Bioinformatic analysis of the date palm genome revealed nine oleosin-like, five caleosin-like, and five steroleosin-like sequences, with predicted structures having putative lipid-binding domains that match their LD stabilizing roles and use as bio-based encapsulation systems. Transcriptomic analysis of date palm seedlings exposed to TCDD showed strong up-regulation of several caleosin and steroleosin genes, consistent with increased LD formation. The results suggest that the plant LDs could be used in ecological remediation strategies to remove POPs from aquatic environments. Recent reports suggest that several fungal and algal species also use LDs to sequester both external and internally derived hydrophobic toxins, which indicates that our approach could be used as a broader biomimetic strategy for toxin removal.

Diagnostic utility of whole body Dixon MRI in multiple myeloma: A multi-reader study

Objective To determine which of four Dixon image types [in-phase (IP), out-of-phase (OP), fat only (FO) and water-only (WO)] is most sensitive for detecting multiple myeloma (MM) focal lesions on whole body MRI (WB-MRI) images. Methods Thirty patients with clinically-suspected MM underwent WB-MRI at 3 Tesla. Unenhanced IP, OP, FO and WO Dixon images were generated and read by four radiologists. On each image type, each radiologist identified and labelled all visible myeloma lesions in the bony pelvis. Each identified lesion was compared with a reference standard consisting of pre- and post-contrast Dixon and diffusion weighted imaging (read by a further consultant radiologist) to determine whether the lesion was truly positive. Lesion count, true positives, sensitivity, and positive predictive value were compared across the four Dixon image types. Results Lesion count, true positives, sensitivity and confidence scores were all significantly higher on FO images than on IP images (p>0.05). Discussion FO images are more sensitive than other Dixon image types for MM focal lesions, and should be preferentially read by radiologists to improve diagnostic accuracy and reporting efficiency.

Highlights from the ISCB Student Council Symposia in 2016

This editorial provides a brief overview of the 12th International Society for Computational Biology (ISCB) Student Council Symposium and the 4th European Student Council Symposium held in Florida, USA and The Hague, Netherlands, respectively. Further, the role of the ISCB Student Council in promoting education and networking in the field of computational biology is also highlighted.

Specific Caleosin/Peroxygenase and Lipoxygenase Activities Are Tissue-Differentially Expressed in Date Palm (Phoenix dactylifera L.) Seedlings and Are Further Induced Following Exposure to the Toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin

Two caleosin/peroxygenase isoforms from date palm, Phoenix dactylifera L., PdCLO2 and PdCLO4, were characterized with respect to their tissue expression, subcellular localization, and oxylipin pathway substrate specificities in developing seedlings. Both PdCLO2 and PdCLO4 had peroxygenase activities that peaked at the mid-stage (radicle length of 2.5 cm) of seedling growth and were associated with the lipid droplet (LD) and microsomal fractions. Recombinant PdCLO2 and PdCLO4 proteins heterologously expressed in yeast cells were localized in both LD and microsomal fractions. Each of the purified recombinant proteins exhibited peroxygenase activity but they were catalytically distinct with respect to their specificity and product formation from fatty acid epoxide and hydroxide substrates. We recently showed that date palm CLO genes were upregulated following exposure to the potent toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Hanano et al., 2016), and we show here that transcripts of 9- and 13-lipoxygenase (LOX) genes were also induced by TCDD exposure. At the enzyme level, 9-LOX and 13-LOX activities were present in a range of seedling tissues and responded differently to TCDD exposure, as did the 9- and 13-fatty acid hydroperoxide reductase activities. This demonstrates that at least two branches of the oxylipin pathway are involved in responses to the environmental organic toxin, TCDD in date palm.

The ISCB Student Council Internship Program: Expanding computational biology capacity worldwide

Education and training are two essential ingredients for a successful career. On one hand, universities provide students a curriculum for specializing in one’s field of study, and on the other, internships complement coursework and provide invaluable training experience for a fruitful career. Consequently, undergraduates and graduates are encouraged to undertake an internship during the course of their degree. The opportunity to explore one’s research interests in the early stages of their education is important for students because it improves their skill set and gives their career a boost. In the long term, this helps to close the gap between skills and employability among students across the globe and balance the research capacity in the field of computational biology. However, training opportunities are often scarce for computational biology students, particularly for those who reside in less-privileged regions. Aimed at helping students develop research and academic skills in computational biology and alleviating the divide across countries, the Student Council of the International Society for Computational Biology introduced its Internship Program in 2009. The Internship Program is committed to providing access to computational biology training, especially for students from developing regions, and improving competencies in the field. Here, we present how the Internship Program works and the impact of the internship opportunities so far, along with the challenges associated with this program.

The Peroxygenase Activity of the Aspergillus flavus Caleosin, AfPXG, Modulates the Biosynthesis of Aflatoxins and Their Trafficking and Extracellular Secretion via Lipid Droplets

Aflatoxins (AF) are highly detrimental to human and animal health. We recently demonstrated that the Aspergillus flavus caleosin, AfPXG, had peroxygenase activity and mediated fungal development and AF accumulation. We now report the characterization of an AfPXG-deficient line using reference strain NRRL3357. The resulting fungal phenotype included a severe decrease in mycelium growth, failure to sporulate, and reduced AF production. Increasing cellular oxidative status by administration of hydrogen peroxide and cumene hydroperoxide did not restore the AfPXG-deficient phenotype, which suggests that AfPXG-deficiency is not directly related to oxidative stress. To investigate possible alternative roles of AfPXG, a gain of function approach was used to overexpress AfPXG, with the reporter gene Gfp, in an AfPXG-deficient line, termed AfPXG+. The resulting phenotype included elevated numbers of stable lipid droplets (LDs) plus enhanced AF production. Highly purified LDs from AfPXG+ cultures sequestered AF and this ability was positively correlated with overall LD number. Site-specific mutagenesis of AfPXG to delete Histidine 85 (AfPXGHis85), a residue essential for its catalytic activity, or deletion of the putative LD targeting domain (AfPXGD126-140), showed that AfPXG-peroxygenase activity was required for AF biosynthesis and that integration of AF into LDs was required for their export via a LD-dependent pathway. Ectopic expression in fungal cells of the plant LD-associated protein, oleosin, also resulted in both additional LD accumulation and enhanced AF secretion. These results suggest that both fungal LDs and their associated caleosin proteins are intimately involved in the biosynthesis, trafficking, and secretion of AF.

Evolutionary and genomic analysis of the caleosin/peroxygenase (CLO/PXG) gene/protein families in the Viridiplantae

Bioinformatics analyses of caleosin/peroxygenases (CLO/PXG) demonstrated that these genes are present in the vast majority of Viridiplantae taxa for which sequence data are available. Functionally active CLO/PXG proteins with roles in abiotic stress tolerance and lipid droplet storage are present in some Trebouxiophycean and Chlorophycean green algae but are absent from the small number of sequenced Prasinophyceaen genomes. CLO/PXG-like genes are expressed during dehydration stress in Charophyte algae, a sister clade of the land plants (Embryophyta). CLO/PXG-like sequences are also present in all of the >300 sequenced Embryophyte genomes, where some species contain as many as 10–12 genes that have arisen via selective gene duplication. Angiosperm genomes harbour at least one copy each of two distinct CLO/PX isoforms, termed H (high) and L (low), where H-forms contain an additional C-terminal motif of about 30–50 residues that is absent from L-forms. In contrast, species in other Viridiplantae taxa, including green algae, non-vascular plants, ferns and gymnosperms, contain only one (or occasionally both) of these isoforms per genome. Transcriptome and biochemical data show that CLO/PXG-like genes have complex patterns of developmental and tissue-specific expression. CLO/PXG proteins can associate with cytosolic lipid droplets and/or bilayer membranes. Many of the analysed isoforms also have peroxygenase activity and are involved in oxylipin metabolism. The distribution of CLO/PXG-like genes is consistent with an origin >1 billion years ago in at least two of the earliest diverging groups of the Viridiplantae, namely the Chlorophyta and the Streptophyta, after the Viridiplantae had already diverged from other Archaeplastidal groups such as the Rhodophyta and Glaucophyta. While algal CLO/PXGs have roles in lipid packaging and stress responses, the Embryophyte proteins have a much wider spectrum of roles and may have been instrumental in the colonisation of terrestrial habitats and the subsequent diversification as the major land flora.

Reflections on a journey: a retrospective of the ISCB Student Council symposium series

This article describes the motivation, origin and evolution of the student symposia series organised by the ISCB Student Council. The meeting series started thirteen years ago in Madrid and has spread to four continents. The article concludes with the highlights of the most recent edition of annual Student Council Symposium held in conjunction with the 25th Conference on Intelligent Systems for Molecular Biology and the 16th European Conference on Computational Biology, in Prague, in July 2017.

Highlights of the 2 nd Bioinformatics Student Symposium by ISCB RSG-UK

Following the success of the 1 st Student Symposium by ISCB RSG-UK, a 2 nd Student Symposium took place on 7 th October 2015 at The Genome Analysis Centre, Norwich, UK. This short report summarizes the main highlights from the 2 nd Bioinformatics Student Symposium.