In the Bioinspired Health and Medicine Section we work with nature to enhance human health and fight diseases. Weather it is getting inspiration from cicadas on how to make antibacterial surfaces or it is evolving proteins to specific therapeutic functions, biological systems have developed a plethora of tools to thrive, self-heal, regenerate, fight microbes etc.
A big part of projects in this section uses synthetic biology to approach the system from within and solve the problems by working with the systems own building blocks, DNA, RNA and proteins, to improve it and heal it.
Stem cell niches: tissue self renewal and therapeutics
Tissue homeostasis and regeneration are critically dependent on a limited number of adult stem cells, their self-renewal capability and their commitment to differentiated cells. Due to these unique properties, stem cells hold enormous potential for the treatment of many diseases. Adult stem cells reside in specialized niches that protect stem cells from rapid differentiation and regulate the delicate balance between self-renewal and differentiation. The mechanisms by which niches regulate stem cells remain poorly defined in mammals, mainly because of the difficulties in manipulating these intricate microenvironments in vivo.
We develop novel technologies to biochemically and structurally deconstruct in vivo niches, and reconstruct them in vitro, creating well-defined artificial stem cell niches as novel paradigms to decipher adult stem cell regulation. This research will yield insights into the dynamics of stem cell fate changes in response to extrinsic protein signals, and may spawn new strategies for tissue engineering and stem cell-based therapies, for example the robust expansion of rare hematopoietic stem cells for the treatment of blood cancers.
For additional conceptual information, please read a review paper in Nature.
Biocompatible scaffolds for tissue engineering
Aim of the projects are to develop degradable and biocompatible scaffolds for tissue engineering. Bioresorbable scaffolds, i.e. porous constructs, seeded with the appropriate type of cells will provide a template for tissue regeneration, while slowly resorbing, to finally leaving no foreign substances in the body, thus reducing the risk of inflammation and offering more cost effective solutions. Polymers are combined with ceramic prior to be physically foamed or fibres are placed by 3D printing to elaborate various porous and anisotropic biocomposites.
This projects is funded by SNF, more detials can be found here: http://p3.snf.ch/project-150190#
Research Lab: prof. Pierre-Etienne Bourban, Laboratoire de technologie des composites et polymères, in collaboration with the Laboratory of Biomechanical Orthopedics (LBO) at EPFL and the Centre Hospitalier Universitaire Vaudois (CHUV).
Biomimetic Models for Fibrous Tissue Repair.
· In In collaboration with Univ. of Pennsylvanian we have developed a three-dimensional micro tissue culture that mimics the healing process more closely than the traditional two-dimensional culture of cells that researchers have long used. First, the research team bioengineered a unique cell culture system in which 3D microtissues are formed from wound repairing cells called fibroblasts embedded in a matrix of collagen fibers, similar to how they exist in the human body. Next, Selman Sakar from the Swiss Federal Institute of Technology in Lausanne and Jeroen Eyckmans, senior postdoctoral associate in Chen’s Tissue Microfabrication Lab, leading authors of this study, cut tiny holes in the microtissues and captured time-lapse videos of the reaction under a microscope. The images showed the fibroblast cells closing the gap and healing the tissue without any signs of scarring. The process of healing observed in these microtissues was surprisingly different from healing previously observed in cells cultured on traditional 2D surfaces.
Research Lab: Microbiorobotic Systems Laboratory, prof. Selman Sakar
Engineering Biological Systems
In our lab we are interested in learning how biological systems use DNA to program sophisticated biological functions and systems. We are also interested in developing new engineering approaches to allow us to engineer biologically systems more efficiently. To make progress in these areas we established an interdisciplinary lab that works at the interface of engineering and the life sciences, combining expertise in biochemistry and cell biology with microfluidic technology and engineering principles. Current projects include the development of an integrated cell-based biosensor for environmental monitoring, the development of artificial cells, and protein engineering.
Designing therapeutic proteins
Our group is driven by the passion of expanding nature’s repertoire by designing novel functional proteins to be used for practical purposes such as therapeutics, vaccines, biosensors and others.
The Fold From Loops (FFL) algorithm was devised to fold and design functional proteins. The major strength of this algorithm, besides speed and accuracy, is the ability to generate conformational ensembles that enable an efficient search for the best amino-acid sequences to yield fully functional proteins. Our laboratory is active in the development of FFL and other algorithms.
Relevant references: Correia B et al. Nature (2014), Procko E et al. Cell (2014)
Protein engineers have extensively used in vitro evolution techniques to alter and refine protein functionality. As any technique in vitro evolution has its own set of limitations, an important aim in at the LPDI is to develop computational algorithms that can guide in vitro evolution experiments improving its feasibility and efficiency.
Relevant references: Azoitei et al Science (2011), Procko E et al Cell (2014)
Up to today, many pathogens still carry a high disease burden and remain elusive to prevention by means of vaccination. New approaches for the development of efficacious vaccines are one of the most pressing needs of our society. In the past, we have had important breakthroughs on the design of novel immunogens that can serve as the foundation of a vaccine for the Respiratory Syncytial Virus (RSV).
Relevant references: Correia BE et al. Nature (2014)
Engineering Metabolic Systems
Living organisms utilize enzyme-catalyzed reactions to synthesize a large array of complex molecules. Enzyme catalyzed processes are characterized by mild conditions, fast reaction rates, highly stereospecific interactions, and minimal toxic byproduct formation. However, living organisms often consist of thousands of metabolites undergoing thousands of reactions. These reactions are carefully regulated through mechanisms developed over millions of years of evolution. An understanding of this complex system and regulation will enable the engineering of enzymes and pathways for the biosynthesis of industrial chemicals or novel pharmaceuticals. The objective of this project is the development of a computational framework for the discovery and the rational design of novel biosynthetic pathways for the production of useful or novel chemicals
Fighting malaria through metabolism
Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA).This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention.
Research article: PLOS Computational Biology 2017., https://doi.org/10.1371/journal.pcbi.1005397
Myoelectric prosthetic hands and fingers allow limb amputees to regain the ability to perform several tasks involved in every day living, representing a significant functional gain. Despite these advantages, they are often rejected by patients. Amongst the most common reasons cited for this reaction is the lack of sensory feedback associated with currently available prostheses, forcing users to rely on vision to guide their movements. One of the major goals in the development of future upper limb prostheses is thus the addition of sensory feedback. We pursue two parallel approaches for restoring touch in upper limb amputees: an invasive approach (using TIME electrodes implanted into the nerves), and a noninvasive approach (where we use electrodes placed on the surface of the skin).
EPFL news article for more information regardin the lates Bionic Fingertip: https://actu.epfl.ch/news/amputee-feels-texture-with-a-bionic-fingertip-5/
Research Lab: prof. S. Micera, Translational Neural Engineering Lab
Functionally graded antimicrobial surfaces
In nature a vast diversity of functions rely on graded architectures, with continuous spatial changes of composition and morphologies. Synthetic functionally graded materials represent one of the many novel integrative and bio-inspired strategies as alternatives to conventional polymer processing and soft chemistry routes to produce hybrid organic/inorganic composites hierarchically organized in terms of structure and functions. Based on the principles of functionally graded properties and self-assembly, we created antibacterial surfaces with outstanding activity. These surfaces are made of graded polymer composites with controlled concentration profiles of photocatalytic Fe3O4@TiO2 core–shell nanoparticles. A photo-magnetophoretic process was invented to generate these surfaces. We also produced super-hard polymer-based surfaces, graded permittivity insulators and low stress coatings using this technique.
Cicade’s wings inspired antimicrobial surfaces
Cicada wings antibacterial nanosurfaces. Anti-microbial contamination of surfaces is a central challenge in medical and industrial applications. Conventional bio-chemical approaches rely on the coatings of biocidal sub-stances such as silver and antibiotics. Despite their wide use in various fields, chemical toxicity, antimicrobial durability and antimicrobial resistance remain critical problems. Alternatively, biophysical approaches prevent bacterial contamination by either anti-adhesive repelling or direct contact killing via micro/nanoscale surface topographies. Recently, nanopillar structures of natural cicada’s wings were found to be deadly to Gram negative bacteria by mechanically tearing the attached cells apart. Inspired by the well-defined nanostructures of cicada’s wings, several synthetic types of nanostructures were fabricated: nanopillars, nanorings and nanonuggets. It was found that all the Au nanostructures, regardless their shapes, exhibited similar excellent antibacterial properties. Our micro/nano-fabrication process is a scalable approach based on cost-efficient self-organization and provides potential for further developing functional surfaces to study the behavior of microbes on nanoscale topographies.
Reference: Wu et al, 2016. Antibacterial Au nanostrcutured surfaces, Nanoscale, 8, 2620, DOI: 10.1039/c5nr06157a