Protein engineering strategy for the stabilization of HIV-1 α-helical peptides

2019 Spring.Includes bibliographical references.Many disease-relevant protein-protein interactions (PPIs) contain an alpha helix and helical binding cleft at their interface. Disruption of these interactions with helical peptide mimics is a validated therapeutic strategy. However, short peptides typically do not fold into stable helices, which significantly lowers their in vivo stability. Researches have reported methods for helical peptide stabilization but, these approaches rely on laborious, and often expensive, chemical synthesis and purification. The research I have preformed aims to stabilize disease-relevant helices through protein engineering. In contrast to chemically constrained helical peptides, a protein can be expressed in a cellular system on a much larger scale. Recently, we reported a new strategy termed "helix-grafted display" that overcomes the traditional hurdles of helical mimics and applied it to the challenge of suppressing HIV entry. Our helix grafted proteins, potently inhibits formation of the extracellular PPI involving C-peptide helix, and HIV gp41 N-peptide trimer, as tested in HIV CD4+ cells. Further optimization of the helical sequence by yeast display yielded new proteins that suppress HIV-1 entry and express substantially better in E. coli. Furthermore, fusion proteins designed to improve the serum stability of these helix grafted proteins have been made that potently suppress HIV-1 entry. Collectively, I report a potential cocktail of evolved HIV-1 entry inhibitors that are functional against an Enfuvirtide-resistant strain and are designed for serum stabilities that rival current monoclonal antibody drugs

Enabling planetary science across light-years. Ariel Definition Study Report

Ariel, the Atmospheric Remote-sensing Infrared Exoplanet Large-survey, was adopted as the fourth medium-class mission in ESA's Cosmic Vision programme to be launched in 2029. During its 4-year mission, Ariel will study what exoplanets are made of, how they formed and how they evolve, by surveying a diverse sample of about 1000 extrasolar planets, simultaneously in visible and infrared wavelengths. It is the first mission dedicated to measuring the chemical composition and thermal structures of hundreds of transiting exoplanets, enabling planetary science far beyond the boundaries of the Solar System. The payload consists of an off-axis Cassegrain telescope (primary mirror 1100 mm x 730 mm ellipse) and two separate instruments (FGS and AIRS) covering simultaneously 0.5-7.8 micron spectral range. The satellite is best placed into an L2 orbit to maximise the thermal stability and the field of regard. The payload module is passively cooled via a series of V-Groove radiators; the detectors for the AIRS are the only items that require active cooling via an active Ne JT cooler. The Ariel payload is developed by a consortium of more than 50 institutes from 16 ESA countries, which include the UK, France, Italy, Belgium, Poland, Spain, Austria, Denmark, Ireland, Portugal, Czech Republic, Hungary, the Netherlands, Sweden, Norway, Estonia, and a NASA contribution

Correction: Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry

<p>Correction: Alternating Hemiplegia of Childhood: Retrospective Genetic Study and Genotype-Phenotype Correlations in 187 Subjects from the US AHCF Registry</p

Ages at unsupported sitting acquisition in each group of patients defined by their genotype.

<p>Cumulative probability of acquiring unsupported sitting by patients presenting the E815K mutation, compared to patientsmutation (3b). Patients with the E815K mutation are likely to gain unsupported sitting at a later age than patients in each of the other groups (respectively P = 0.0002 and P = 0.0020).</p

Ages at onset of AHC in each group of patients defined by their genotype.

<p>The horizontal lines in the boxes indicate the 25th percentile (bottom), the median (middle) and the 75 percentile (top) values. Crosses indicate the mean values. Numbers of patients analyzed in each group are indicated above the boxes.</p

Odds ratio for occurrence of status epilepticus in AHC patients with different <i>ATP1A3</i> mutations.

<p>Odds ratio for occurrence of status epilepticus in AHC patients with different <i>ATP1A3</i> mutations.</p