Dear colleagues, We have open at BCAM in Bilbao two positions: one PostDoc and one Research technician. The Research technician is intended as a bridge contract after the Master and before to start a PhD. The deadline for both positions is the 16th of December 2022, here are the corresponding links:

Postdoc. Research program "Stochastic Modelling and Simulation of Anomalous Diffusion" http://www.bcamath.org/en/research/job/ic2022-10-postdoctoral-fellow-on-effe... http://www.bcamath.org/en/research/job/ic2022-10-postdoctoral-fellow-on-effective-treatment-strategies-for-rare-diseases-based-on-gene-therapy-bmtf

Research technician. Research program "Data Analysis for Anomalous Diffusion in Biological Media" http://www.bcamath.org/en/research/job/ic2022-10-research-technician-on-effe... http://www.bcamath.org/en/research/job/ic2022-10-research-technician-on-effective-treatment-strategies-for-rare-diseases-based-on-gene-therapy-bmtf

For any question, you can get in contact with me: gpagnini@bcamath.org mailto:gpagnini@bcamath.org Below you can read a cut & paste of the research program. Thank you very much. Sincerely, Gianni

Ps: further open positions at BCAM can be found at http://www.bcamath.org/en/research/job http://www.bcamath.org/en/research/job

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Effective treatment strategies for rare diseases based on gene therapy Project summary Gene therapy medicinal products (GTMPs) are one of the most promising biopharmaceuticals, which are beginning to show encouraging results. Gene therapy based on the administration of DNA, messenger RNA (mRNA) or short-hairpin RNA (shRNA) are intended for gene augmentation or gene suppression, whereas the use of small interfering RNA (siRNA), microRNA, antisense oligonucleotides (ASOs) or aptamers provides posttranslational gene silencing. The efforts and advances made in this area have led to the development of new therapeutic strategies to treat several disorders, many of them without currently available treatments, as rare diseases. A key challenge for the clinical application of nucleic acid medicinal products entails the availability of delivery systems specifically adapted to their features and purpose. For a successful gene therapy, the delivery systems have to protect the genetic material from degradation, facilitating its internalization in target cells and releasing them intracellularly. The first step for an efficient internalization of the nucleic acid is the interaction between the delivery system and the cell membrane. Therefore, the understanding of the intracellular behaviour of the nanodelivery systems, the nucleic acid they carry (mRNA, DNA, siRNA, shRNA or ASO) and the endosomes after the internalization process will allow to advance in the design of nucleic acid based-nanomedicines aiming to improve the effectiveness of gene therapy treatments, by developing strategies for an improved intracellular delivery and endosomal escape.

The issue of physical understanding and mathematical modelling of nanodelivering is still an open problem. As a matter of fact, anomalous diffusion emerged in living systems, namely, diffusing particles do not follow rules and properties of Brownian motion, and delivering by nanoparticles also goes according to anomalous diffusion such that modelling and understanding of anomalous diffusion is fundamental for gene therapy improvement. Therefore, new and advanced techniques are required for modelling such random motions and further studies needed for the understanding of the underlying statistical physics. It is well-known that anomalous diffusion is strongly related with fractional diffusion equations that are differential equations involving integral operators defined within the branch of mathematical analysis named Fractional Calculus. Under the point of view of statistical physics, these systems show not classical features as, for example, long-range correlations, power-law distributions, weak ergodicity breaking and aging. This framework calls for stochastic processes in inhomogeneous media and/or for heterogeneous ensembles of particles and then within the families, for example, of scaled Brownian motion and diffusing-diffusivity as well as those of the generalized gray Brownian motion and the superstatistical fractional Brownian motion, in general, and their under-damped extension.

In general, the project aims to assess in deep the intracellular behavior of lipid nanoparticles for nucleic acid delivery for establishing models of anomalous diffusion useful to optimize the nanomedicines since the first steps of development. An important step towards further progress in the clinical application of gene therapy is expected and the results be applied in a number of delivery systems and diseases.

The project will be mainly focused on the following rare diseases: Rare metabolic diseases; Rare retinal degenerative diseases; CAR therapy in pediatric acute leukemia, that are currently investigated by the PharmaNanoGene group at the Faculty of Pharmacy (UPV/EHU) and Bioaraba Health Research Institute. The development of the proper stochastic processes for nanodelivering and the interpretation of the corresponding statistical physics will be conducted by the Statistical Physics group at BCAM led by the proponent Ikerbasque Research Associate Gianni Pagnini has decades of experience in the field of fractional diffusion equations and the development of the related models, while the molecular simulations and advanced data analysis will be provided by the Mathematical, Computational and Experimental Neuroscience group at BCAM led by Ikerbasque Professor Serafim Rodrigues.

— Gianni Pagnini Ikerbasque Research Associate BCAM - Basque Center for Applied Mathematics Alameda de Mazarredo, 14 E-48009 Bilbao, Basque Country - Spain Tel. +34 946 567 842 gpagnini@bcamath.org | www.bcamath.org/gpagnini

( matematika mugaz bestalde )