Model of Dicer depletion in the otocyst

Previous studies have demonstrated the importance of Dicer during early cochlear development.

To extend this investigation to the establishment and differentiation of the prosensory domain, researchers at GIGA crossed Dicerflox/flox mice with FoxG1Cre/+ mice to generate embryos (i.e., FoxG1:Dicer-cKO) with an early (E8.5) depletion of Dicer in the otocyst.

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Ototoxic drug-treated animal

Typically, the cochlear effects of ototoxic drugs are studied in the guinea pig, which is the most common animal model used in hearing research.

In this model, guinea pigs receive an intrapritoneal injection of either Knamycin during 7 days or Cisplatin during 10 days.

Cisplatin- and aminoglycoside-induced ototoxicity is known to be mediated via injury to several terminally differentiated cellular targets in the cochlea, including the marginal and intermediate cells of the stria vascular.

To quantitatively assess hearing loss in toxic drug-treated animals, the Auditory Brainstem Responses (ABR) are measured weekly.

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Guinea pigs deafened by aminoglycoside

Guinea pigs deafened by aminoglycoside are a model of neuronal degeneration secondary to hair cell destruction in the organ of Corti.

In this model, the left ear is operated on and the right ear is used as control (untreated ear, no operations). Each left bulla is opened under sterile conditions through a retro-auricular approach. The cochlea is exposed ventrally and opened using a 26 gauge needle. A catheter is inserted and connected to an electrical Hamilton syringe pump. The aminoglycoside gentamicin is administered at a concentration of 50 mg/ml for the cochlear lesion (25 ml of gentamicin in 5 min). Using the same cochlear opening, a catheter inserted and connected to a subcutaneous osmotic pump filled with products to be tested and dissolved in artificial perilymph solution.

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Cells regeneration

Researchers at GIGA have demonstrated that mammalian hair cells can be directly generated from supporting cells by inhibition of ephrin-B2 signaling.
Using either ephrin-B2 conditional knockout mice, shRNA-mediated gene silencing or soluble inhibitors, they found that downregulation of ephrin-B2 signalling at embryonic stages results in supporting cell translocation into hair cell layers and subsequent switch in cell phenotype from supporting cell to hair cell.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Role of ELP3

Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency.

Given the importance of acetylation homeostasis in controlling developmental processes together with recent reports implicating Elp3 in cortical neurogenesis, researchers at GIGA investigated its role during inner ear formation.

Using different knock-out mouse models, they have shown that Elp3 enzyme is crucial for neuronal survival in the spiral ganglion and in the vestibule and that it ensures a correct innervation pattern in the developing inner ear. In the absence of Elp3, a drastic increase in the number of apoptotic neurons particularly during the early stages of development (between E12.5 and E14.5). Postnatally, the neurons remaining in Elp3cKO cochleae seem to establish synaptic contacts with the sensory cells but show obvious signs of cell damage.

Furthermore, they identified a severe hearing loss in Elp3cKO mice through Auditory Brainstem Response.

Taken together, these data support a role for Elp3 in hearing and balance and point out an important role for acetylation homeostasis during inner ear formation.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Stability testing

Stability testing is performed after storage in defined conditions according to standard and accelerated ICH conditions. We provide you with different range of storage conditions. All storage rooms are fully-controlled with 24/7 monitoring and alert systems.

Our services include:

  • Support in designing studies for real-time
  • Development and validation of “stability indicating methods”
  • Examination of stability-relevant parameters (temperature – humidity)
  • Interim reports for every testing period
  • Comprehensive final report

Looking for clinical advice or support, or preparing for a clinical study? We will help you set up a cost-effective and time-efficient study! Get in touch with our experts [info@b2h.be].

Drug administration & Patient monitoring

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  • Centralized clinical unit with 30 equipped hospital beds
  • Experience in running different study types and trial design
  • Different types of drugs like NCE and NBE
  • Database of more than 2.700 healthy and reliable volunteers
  • Privileged access to medical and technical expertise of CHU and ULg (such as Cyclotron, GIGA, CIP, Sleep Center, Pain clinic…)

We offer you a professional and scientific support to conduct clinical trials and the decision making processes during the early phases of the development of new molecules. This includes clinical pharmacology trials giving an insight into a drug candidate’s safety, tolerability, pharmacokinetics and pharmacodynamics.

Looking for clinical advice or support, or preparing for a clinical study? We will help you set up a cost-effective and time-efficient study! Get in touch with our experts [info@b2h.be].


Induced pluripotent cells

One team of the GIGA has developed an artificial sensory epithelia or “Mini Ear” in vitro model mimicking the in vivo organ equivalent.

For this purpose, otic progenitor cells (hOPCs) were generated using a reproducible protocol based on the differentiation of human induced pluripotent stem (hiPS) cells. Those hOPCs are at least 90% homogenous and can be frozen and thaw ad libitum. Those cells can be further differentiated towards inner ear hair cells using a stepwise method mimicking inner ear development.

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Bio-analysis

  • Standard biology analysis: certification for more than 550 tests, 17025 and 15189 ISO standards and BELAC accreditation
  • Development of personalized drug monitoring
  • Determination of IMP, metabolites and drug residues in different biological matrices
  • PK, PD and immunogenicity testing

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Looking for clinical advice or support, or preparing for a clinical study? We will help you set up a cost-effective and time-efficient study! Get in touch with our experts [info@b2h.be].

Preclinical imaging

Our GIGA platforms offer advanced preclinical functional and anatomical imaging solutions for a broad spectrum of application fields.

Our range of techniques includes:

Magnetic resonance imaging (MRI) scanners use strong magnetic fields and radio-waves to visualize detailed internal structures. Images are obtained in vivo with very high spatial and temporal resolution, good contrast for brain and soft tissues. MRI can be used in a wide variety of applications including anatomical, functional (fMRI) and molecular imaging for medical diagnosis, staging of disease and for follow-up without exposure to ionizing radiation.

Our system, Agilent MicroMRI 9,4T 310 ASR, is equipped with a technical imaging unit (MINERVE). It ensures the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

Contact [info@b2h.be] us to discuss how these capabilities can forward your projects! We will help you develop tailored solutions.

Computed Tomography (CT) is a non-destructive technique that yields structural and anatomical high-resolution 3D images with limited or no sample preparation required. This imaging modality complements the metabolic or functional images obtained with PET.

Being equipped with two beds for mice (25 mm) and rats (75 mm), our system, the TriFoil Imaging eXplore CT 120 micro-CT, is designed to visualize, quantify and characterize anatomical parameters in small animals. The system is also equipped with a technical imaging unit (MINERVE), ensuring the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

Contact [info@b2h.be] us to discuss how these capabilities can forward your projects! We will help you develop tailored solutions.

Positron Emission Tomography (PET) has the sensitivity at picomolar level to visualize molecular processes in 3D. In vivo PET imaging with labelled lead compounds will help to select the best one for clinical trials.

 

The technique allows:

  • The collection of quantitative and dynamic biodistribution data (e.g. micro-dosing studies) at an early stage of the clinical development: dynamic data for in-depth kinetic modeling, online blood measurements and in-brain positron-emission measurements
  • Detailed drug occupancy studies (proof of targets, mechanism, efficacy, pharmacokinetics, biodistribution)
  • Concentration analysis of targeted analytes after having developed and validated a dedicated method using microdialysis, a technique used for continuous measurement of free, bound analyte concentrations in the extracellular fluid. Analytes may include endogenous molecules (e.g. neurotransmitter, hormones, glucose, etc.) to assess their biochemical functions in the body, or exogenous compounds (e.g. pharmaceuticals) to determine their distribution within the body)

We are authorized to conduct research programs with classical (18F-FDG) and original radiotracers. Furthermore, we have developed expertise in experimental design, data collection, correction and modeling for kinetic analysis.

Being equipped with two beds for mice (25 mm) and rats (75 mm), our system, the Siemens Concorde FOCUS 120 micro-PET, is designed to visualize, quantify and characterize anatomical parameters in small animals. The system is also equipped with a technical imaging unit (MINERVE), ensuring the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

Contact [info@b2h.be] us to discuss how these capabilities can forward your projects! We will help you develop tailored solutions.

Our equipment includes the high-resolution, high-frequency ultrasound imaging system Vevo 2100 (Visualsonics). This is a non-invasive, in vivo micro imaging system, enabling visualization, assessment and measurement of anatomical structures and hemodynamic function in longitudinal studies for small animal phenotyping.

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The Xenogen IVIS 200 system is a highly sensitive and flexible system to trace bioluminescent reporter genes both in vivo and in vitro. It allows non-invasive longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals. By performing spectral fluorescence imaging, it allows the simultaneous use of bioluminescence and fluorescence imaging.

Bioluminescence imaging uses the enzyme, luciferase, that can be inserted into the genome of cancer cells or the cells you wish to track. Once these cells are implanted within mice, a tail vein or intra-peritoneal injection of luciferin (luciferase substrate) allows to follow their distribution ex vivo without euthanasia.

Contact [info@b2h.be] us to discuss how these capabilities can forward your projects! We will help you develop tailored solutions.

Intravital microscopy is an extremely powerful tool that enables imaging several biological processes in living animals. In particular, to analyze:

 

 

  • Recruitment processes of leukocytes and platelets on microvessel endothelia
  • Bacterial adhesion on the microvessel endothelia
  • Thrombi and vascular occlusion formation
  • Lymphocytes migration to lymph nodes and lymphocytes adhesion to endothelia

Our equipment includes a motorized Olympus Cell R (Upright) microscope with EMCCD camera, controlled via the Slidebook software.

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PXI X-RAD SmART Image Guided Irradiator combines 3D imaging with highly accurate radiotherapy for Small Animals: mice, rats and rabbits. It combines a user friendly interface with state-of-the-art Monte Carlo calculation algorithms to rapidly devise treatment plans.

The system is fully integrated, with automated CT-CT registration, allowing, Image Guided Radiotherapy for precise tumor/organ localization. The integrated treatment planning enables rapid and highly conformal radiotherapy treatments, with collimator from 1 mm to 10 cm in round and non-round shapes, to be delivered in any scenario, ranging from simple subcutaneous xenografts to complex metastatic models or to develop non tumoral model as radiation-induced injury for a specific purpose.

Contact [info@b2h.be] us to discuss how these capabilities can forward your projects! We will help you develop tailored solutions.