Industrial Internships Available
Merck Research Laboratories (USA)
Therapeutic applications of siRNA silencing employs an endogenous eukaryotic process for suppression of protein expression based on sequence specific catalytic degradation mRNA. Since this novel therapeutic modality opens new possibilities for previously undruggable targets, Merck made a commitment to nurturing the promise of siRNA therapeutics into a viable therapeutic modality as illustrated by the acquisition of Sirna in 2006. Since then the focus of our group has been to understand disposition and pharmacokinetics of siRNA employing different delivery platforms to better understand barriers to siRNA efficacy and toxicity. Characterization of the pharmacokinetics and disposition of siRNA presents unique challenges relative to conventional small molecule drugs. Distribution of small molecules to pharmacological targets is generally mediated by passive equilibration of the free drug across biological membranes. In contrast to conventional drugs, the large size (15 KD) and high charge density of siRNA prevents passive equilibration between the target location and the systemic circulation. siRNA requires a delivery vehicle to facilitate cellular uptake and delivery to the cytosol. Once in the cytosol siRNA irreversibly dissociates upon binding to Ago-2 to form the active RNA silencing complex. As a consequence of these mechanistic and structural differences from conventional drugs, paradigms applied to characterization of small drug molecules may not directly apply to siRNA drug candidates. In particular characterization of siRNA disposition entails evaluation of both the siRNA and delivery vehicle components, pharmacokinetics is indirectly related to pharmacological activity, mechanisms of metabolism differ from conventional drug molecules, and tissue and cellular distribution are strongly influenced by design features incorporated into the delivery vehicle. Projects within our group address these challenges using biochemical, analytical and cell biological and modeling techniques to understand mechanism of tissue tropism, endosomal trafficking and cytosolic delivery, PK/PD, and biotransformation of delivery vehicles and siRNA.
Eligibility: Only funded Trainees in the program are eligible to apply.
If you are interested, please contact biotherapeutics@utoronto.ca
GlaxoSmithKleine
Regulatory Affairs Intern
Every second, 30 people around the world are inoculated with a GlaxoSmithKline vaccine; every minute, 1,100 people receive a prescription for one of our products; every hour, GlaxoSmithKline spends half a million dollars on research and development. Would you like to participate in defining the future of the pharmaceutical industry? Then join us in our quest to improve the quality of human life.
We are searching for bold, decisive, innovative team players to add value to Canada's premier pharmaceutical company. If you are an energetic, career-minded professional with a passion for leadership, a focus on solutions, and a commitment to outstanding performance, we invite you to apply to our exciting and rewarding role.
If you are interested in a career in Regulatory Affairs, this internship with GlaxoSmithKline may be the right opportunity for you. In this role, you will be assisting with various submission related activities and other projects within the Regulatory Department
Awarded to Diane Cockburn, Graduate Student, Biological Therapeutics Trainee.
Lorus Therapeutics Inc.
Lorus Therapeutics Inc. is a biopharmaceutical company specializing in the research and development of pharmaceutical products and technologies for the management of cancer. An internship is available to assist in the in vivo testing of novel formulations of the cytokine IL-17E, which Lorus is developing for cancer treatment. Lorus has shown that IL-17E has potent antitumor activity when injected into mouse models of human tumors. Lorus is interested in developing novel formulations of IL-17E to optimize the dosing schedule for this drug candidate and to improve its potential use as a therapeutic entity. In addition to IL-17E, Lorus is interested in identifying a delivery system for LOR-1284, which is a short interfering RNA (siRNA) molecule that targets the R2 subunit of ribonucleotide reductase. Lorus has shown that LOR-1284 has antiproliferative activity in vitro when transfected with lipofectin or oligofectamine. LOR-1284 also has antitumor activity in human tumor xenograft models in mice following intravenous injection of the molecule without a delivery vehicle. As with IL-17E, there is potential to formulate LOR-1284 with a delivery vehicle to improve its drug-like properties. In this internship, Lorus will participate by providing these biomolecules as candidates for formulation in advanced drug delivery platforms. Lorus will interact with trainees through collaboration with the mentor’s laboratory and enable the trainees to gain insight into the drug development process.
Eligibility: Only funded Trainees in the program are eligible to apply.
If you are interested, please contact biotherapeutics@utoronto.ca
MDS Nordion
MDS Nordion leases laboratories from the University of Ottawa Heart Institute to carry out research and development. The research facility is referred to as the Canadian Molecular Imaging Centre of Excellence (C-MICE) and it is dedicated to the development of new tracers for SPECT and PET molecular imaging. Tracer development programs cover cardiology and oncology, and may extend to neurology. A four month internship position is available to a Postdoctoral fellow (preferred) or a graduate student who will participate in the development of new tracers including organic synthesis and radiolabeling of the precursor. The candidate will participate in imaging tracer formulation development and validation of test methods to assess the chemical purity and properties of the tracer (HPLC, UV, NMR, Mass Spectrometry, and Thin Layer Chromatography). The research will investigate tracer biological properties including receptor binding assays, ELISA assays, Western blot, and electrophoresis. Successful biological characterization may lead to carrying out in vivo imaging in small animal models with a NanoSPECT/CT or Inveon 120 PET camera. The project allows interaction with MDS Nordion's C-MICE research team and the opportunity to participate in novel tracer development.
Eligibility: Only funded Trainees in the program are eligible to apply.
If you are interested, please contact biotherapeutics@utoronto.ca
NoAb BioDiscoveries Inc.
NoAb BioDiscoveries Inc. specializes in in vivo pharmacokinetics studies, in vitro ADME assays and ADME-related gene expression assays, offering pharmaceutical and biopharmaceutical clients the ability to profile compounds for selection of the best drug candidates for further pre-clinical and clinical development. In addition to providing these services, the company is involved in a number of research projects, including ones involving academic and industrial collaborators. Two in-house research projects may be available for an industrial internship. The first project involves surveying the effect of the treatment of a biological therapeutic of interest on the expression level of at least 140 ADME-associated genes (involved in metabolism, conjugation and transport) to determine its potential to cause drug-drug interactions in the clinic. This project would utilize our propriety microarray-based technology, DTEx™, in addition to confirmation of effects on select genes by QPCR. The trainee will have the opportunity to design, execute and interpret the results of in vitro (treatment of human cells in culture) and/or in vivo (administration to rats) experiments using such techniques as cell culture and/or rodent dosing and tissue isolation, and molecular biology techniques. The second project involves determining the penetration of a biological therapeutic of interest into the CNS in order to characterize its potential for efficacy and/or toxicity. The trainee will have the opportunity to participate in the design, execution and interpretation of one or more in vivo studies in rodents which may be used in this regard: (1) microdialysis sampling in well defined anatomical locations within the brain to determine the brain extracellular fluid concentrations of the potential therapeutic at or close to the drug target site, (2) serial CSF and plasma collection to characterize penetration of the potential therapeutic across the blood-CSF and/or blood brain barrier (BBB), (3) in situ brain perfusion to determine the uptake of the potential therapeutic across the BBB, or (4) determination of the tissue binding (by equilibrium dialysis) and whole brain concentrations of the biological therapeutic as an estimate of unbound brain concentration. The method(s) used in the project will be dependent on the properties of the biologic therapeutic of interest (eg. size and potential for detection and quantification by LC-MS/MS analysis) and the specific limitations of each of these models. The trainee would gain experience in the design of in vivo experiments and in pharmacokinetics data analysis using software programs such as WinNonlin.
Awarded to Matthew Durk, Graduate Student, Biological Therapeutics Trainee.
ApoPharma
ApoPharma’s immunologically active peptide for the treatment of psoriasis and other autoimmune diseases is currently in phase I clinical trial. Two 4-month internship positions are open within this program for interested candidates. One project focuses on the drug’s mechanism of action. The postdoctoral fellow or graduate student will participate in the design, execution and interpretation of in vitro and in vivo studies using techniques such as human stem cell culture and differentiation, adhesion and migration assays, immunohistochemistry, FACS, and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS, a sensitive technique is used for quantitation of metals). Another project focuses on testing pro-drug candidates for gastric and intestinal stability, in vitro and in vivo oral bioavailability and bioconversion to the parent drug. Trainees will learn how to design in vivo pharmacokinetic studies and gain hands-on experience in bio/analytical HPLC method development. The project also involves the use of advanced software for prediction of physicochemical properties, absorption and pharmacokinetics. Both projects offer an opportunity for interaction with ApoPharma’s scientists of a diverse background and with the outside academic and industrial collaborators. The trainees will also have an opportunity to learn about various aspects of drug development by participating in a multidisciplinary Project Management Team.
Eligibility: Only funded Trainees in the program are eligible to apply.
If you are interested, please contact biotherapeutics@utoronto.ca