In This Issue

doi:10.1073/iti3106103

New Research In

APPLIED BIOLOGICAL SCIENCES

Targeted lentivector for improved gene delivery

Gene therapy uses harmless viruses to introduce a desired gene into a target cell for therapeutic and research purposes, but targeting viruses to specific cell types has been a major challenge in the field. Lili Yang et al. report the development of a flexible and efficient gene therapy method that enhances gene delivery. The authors genetically engineered the lentivirus vector by incorporating two proteins into the viral surface: an antibody specific to the desired target cell and a “fusogen,” or a protein that helps fuse the viral membrane with the target cell. The antibody recognized the desired cell type and helped bind the virus to the target cell, prompting the target cell to engulf the virus. Then, the “fusogen” protein fused the viral surface with the target cell membrane, releasing the viral contents into the target cell. The technique was effective in cultured cells as well as in live, intact mice. Because of the wide availability of antibodies, Yang et al. suggest that this method could be used to aid virus-mediated gene transfer to a broad range of cell types. — M.M.

Figure 1.

Targeting lentivectors.

“Targeting lentiviral vectors to specific cell types in vivo” by Lili Yang, Leslie Bailey, David Baltimore, and Pin Wang (see pages 11479–11484)

BIOPHYSICS

Structural simulation of amyloid fibril bonding

Simulations of a peptide chain that can form amyloid fibrils show how different β-sheet proteins can assemble to form these disease-causing fibers. Luciana Esposito et al. performed a molecular dynamic simulation of the binding interactions between the GNNQQNY motif on separate peptides. This previously discovered motif forms a steric zipper that can link proteins together. Esposito et al. found that the zippers formed by pairs of the β-sheet motif were stable. Although the zipper area was stable, the backbone of each strand showed a significant twist. This characteristic allows both flat and twisted β-sheets to assume configurations that lead to the formation of amyloid fibrils. Esposito et al. also found that two pairs of β-sheets could associate and form stable interactions. This finding can resolve the opposing crystallographic and electron microscopy literature data, the authors say, and these results, overall, may explain how amyloid fibrils can grow into large aggregates. — P.D.

Two pairs of GNNQQNY β-sheets.

“Molecular dynamics analyses of cross-β-spine steric zipper models: β-Sheet twisting and aggregation” by Luciana Esposito, Carlo Pedone, and Luigi Vitagliano (see pages 11533–11538)

GENETICS

Compact, complex genome of tiniest eukaryote

The unicellular green alga, Ostreococcus tauri, is a common member of marine phytoplankton and is the world’s smallest free-living eukaryote, possessing a single mitochondrion and chloroplast. This picoeukaryote belongs to the Prasinophyceae group, an ancient lineage that gave rise to today’s photosynthetic plants. Evelyne Derelle et al. have sequenced and characterized the green alga’s compact 12.56-Mb nuclear genome, which is similar in size to that of much larger yeast. Of the 20 chromosomes comprising its heterogeneous genome, chromosomes 2 and 19 were markedly different, containing 77% of O. tauri’s transposable elements. The authors were able to predict >8,100 protein-coding regions, making the alga the most gene-dense free-living eukaryote. This density is the result of several processes including intergenic compaction, gene fusion events, and a reduction in the size of gene families, eliminating redundant proteins. O. tauri’s proteome reflects its unique position in evolutionary history, with characteristics from diverse species. The carbon assimilation machinery is most similar to that of bacteria, ammonium transporters match those of green lineage algae as well as prokaryotes, and chlorophyll synthesis pathways are similar to those of angiosperms. With its unusual features and downsized gene families, O. tauri may make an ideal model system for studying eukaryotic genome evolution, including chromosome specialization and green lineage ancestry. — F.A.

O. tauri strain OTH95.

“Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features” by Evelyne Derelle, Conchita Ferraz, Stéphane Rombauts, Pierre Rouzé, Alexandra Z. Worden, Steven Robbens, Frédéric Partensky, Sven Degroeve, Sophie Echeynié, Richard Cooke, Yvan Saeys, Jan Wuyts, Kamel Jabbari, Chris Bowler, Olivier Panaud, Benoît Piégu, Steven G. Ball, Jean-Philippe Ral, François-Yves Bouget, Gwenael Piganeau, Bernard De Baets, André Picard, Michel Delseny, Jacques Demaille, Yves Van de Peer, and Hervé Moreau (see pages 11647–11652)

MEDICAL SCIENCES

Turning stem cells into T cells

Human embryonic stem cells (hESCs) hold therapeutic power due to their potential to differentiate into all the cell types of the human body, and the key to tapping that power lies in being able to direct which cell type an hESC will become. Directed differentiation into several hematopoietic lineages, such as B cells, natural killer cells, and macrophages, has been achieved, and Zoran Galić et al. now report a successful differentiation toward the T cell lineage. The authors used a coculture of hESCs and mouse bone marrow stromal cells to initiate differentiation, followed by engraftment of the stem cells into human thymic tissues grown in immunodeficient mice. The expression of an enhanced GFP transgene was maintained throughout differentiation, showing that genetic manipulation of these cells is possible. Galić et al. believe that, with further optimization, this system could provide a ready source of primary human T cells for both basic mechanistic studies and possible treatment of T cell disorders. — N.Z.

Human embryonic stem cell colony.

“T lineage differentiation from human embryonic stem cells” by Zoran Galić, Scott G. Kitchen, Amelia Kacena, Aparna Subramanian, Bryan Burke, Ruth Cortado, and Jerome A. Zack (see pages 11742–11747)

MICROBIOLOGY

Nutrient uptake role of bacterial stalks

Bacteria exhibit a wide variety of cellular shapes, including round, cylindrical, coiled, branched, and star-shaped. However, the relationship of these bacterial morphologies to their biological functions is not fully understood. To elucidate the function of one of these cellular forms, Jennifer Wagner et al. examined the stalk-like projections of Caulobacter crescentus, an aquatic, Gram-negative bacterium. The authors found that, unlike bacterial flagella or pili, C. crescentus’ stalks were true extensions of the organism’s cell body, possessing both peptidoglycan and cell membranes. These stalks were shown to take up and hydrolyze an organic phosphate molecule, suggesting that the stalks act as nutrient uptake antennae for the cell. Mathematical analysis of nutrient uptake by different cell shapes showed that the uptake rate nearly doubled for bacteria with the cylindrical stalk shape, compared with that for other bacterial cell bodies of the same surface area (when nutrient motion was governed by diffusion). According to the authors, such elongated projections minimize the energetic cost of increasing both surface area and volume, thus providing an efficient evolutionary strategy for bacteria to increase their rate of nutrient uptake. — F.A.

Caulobacter crescentus.

“A nutrient uptake role for bacterial cell envelope extensions” by Jennifer K. Wagner, Sima Setayeshgar, Laura A. Sharon, James P. Reilly, and Yves V. Brun (see pages 11772–11777)