Obesity is a worldwide epidemic and a serious public health threat since it greatly increases the risk of highly morbid chronic diseases, including type 2 diabetes, hypertension, cardiovascular disease, and many cancers. A growing body of literature has suggested that obesity is associated with hypogonadism, (defined in males as low levels of endogenous testosterone) a reproductive disorder that substantially elevates metabolic risk. The mechanisms linking reproductive function to metabolism are not fully understood, but emerging evidence from clinical and preclinical studies suggests the potential role of hypothalamic gliosis. Recent data support a model in which microglia (brain macrophages) and astrocytes mediate the effects of a Western-type diet to induce obesity, and that hypogonadism synergizes with an obesogenic diet to profoundly activate hypothalamic gliosis. In this context, we propose a multidisciplinary approach to unveil the potential role of hypothalamic gliosis as a central node linking metabolic dysregulation and reproductive dysfunction. The studies described herein will use astrocyte- and microglia-specific mouse models of increased or reduced inflammatory signaling to determine whether gliosis is proximal to hypogonadism, hypogonadism causes gliosis, or they establish a vicious cycle together. These studies will potentially provide cellular targets for new therapies to offset the long-term metabolic harm from hypogonadism and to improve reproductive function in obese patients. Beyond its translational value, the project will provide a solid foundation for the scientific career of the fellow and help her achieve the long-term goal of becoming an independent scientist.

Because current limitations in 3D bioprinting for tissue engineering stem from the fact that the multi-scaled vasculature associated to the human microtissues and organs cannot be replicated. The overarching aim of the HOT-BIOPRINTING project is to deliver a methodology enabling the manufacturing of a new generation of tissue-like structures with properties mimicking more closely the complexity of biological tissues and organs. The innovation of HOT-BIOPRINTING lies on the development of a disruptive technology named Holographic optical tweezing bioprinting (HOTB) for single and automatized multiple cell 3D bioprinting. The non-contact nature of light will eliminate the fails on bioprinting associated to instrumentation, which along with the HOTB capabilities for manipulating single cells for printing will drive a new paradigm shift: “resolution will be dictated by the cell size instead of by the mechanical component of the instrumentation”. This new technological advancement for resolution enhancement while maintaining bioprinting speed using holographic automatization can open new opportunities to the tissue engineering and regenerative medicine community. I propose the following general objectives that go beyond the state of the art in bioprinting human mimetic tissue: 1) Generate the knowledge and develop a Holographic Optical tweezer bioprinter (HOTB) for high-definition single/multiple cell bioprinting. 2) Demonstration and automatization for 3D multicellular printing for large area tissue generation. 3) Overcome the challenges associated with existing biofabrication techniques (limited multi-scaled vascularization and oversimplified structures). 4) Demonstrating lymph-node bioprinting with integrated vasculature. This represents a big challenge, if achieved, will revolutionize the bioprint technology by increasing the tissue complexity and by responding to the demand of biofabricating multi-scale vascularized complex tissues and organs.

Phytosanitary products are major component of modern agriculture contributing to the substantial increase in yields and crop protection. Their accumulation in the environment presents risks to humans and living beings in front of a spectacular development of resistance to pesticides among target pests and diseases. Thereby, increasing global ecological and economic requirements tend to shift agriculture towards healthier production systems that take into account crop sustainability, environment and human health. Entomopathogenic fungi (EPF) are considered as an ecological alternative to pesticides thanks to several privileges notably their specificity of action, absence of toxic residues and spectacular genetic elasticity. Additional interesting features were recently attributed to entomopathogenic endophytes for plant protection and production. However, data published so far are variable and fail to Predict their bioecological roles accurately. Consequently, through a novel integrated research program, EFFECT will use cutting-edge experiments and analyses to disentangle and valorize the additional ecological roles of EPF in plant structure relating to systematic endophytic development and aggressor’s survival that underpin feedback mechanisms between plant and its ecosystem. The ultimate objective to be achieved is to boost the effectiveness of these micro biocontrol agents in order to make an innovative and feasible substitute to chemical insecticides. In addition to the scientific audience it may interest, the project might offer potential solutions for industrials and farmers to combat many pests and diseases whilst benefiting from ecological aspects to reduce chemical input into the environment. Accordingly, EFFECT combines multidisciplinary approaches to innovatively achieve objectives that are timely and in line with the current European and global research trends of which positive spin-offs will be achievable and measurable on different levels.