The bitter truth of taste receptors hos Biologisk Institut - Københavns Universitet

BACKGROUND

Sweet, umami, and bitter tastes allow us to enjoy homecooked meals, and motivate us to seek out Michelin star restaurants. However, gustatory perception is also tied to survival and helps our bodies identify toxins, maintain nutrition, and regulate gastrointestinal motility. The receptors involved in taste signaling are well-known, but details on their molecular mechanisms remain uncharacterized. The Autzen Lab is working on advancing our understanding of the molecular mechanisms underlying sweet, umami, and bitter taste perception and is looking for motivated students who wants to join the team.

PROJECT DESCRIPTION

The bitter receptor T2R38 is involved in nutrient uptake in the gastrointestinal tract and evasive response to certain toxic substances. A non-functional haplotype of T2R38 is prevalent in Caucasians, causing reduced sensitivity to bitter perception. T2R38 may be important in our understanding of bitter perception and the mechanism underlying body weight regulation. However, structures of bitter receptors remain elusive complicating the pharmacological targeting of T2R38.

In this project you will express and purify the T2R38 bitter receptor, reconstitute it into nanodiscs, complex it with heterotrimeric G proteins, and subject it to single particlecryo-electron microscopy (cryo-EM) to determine its 3-dimensional structure. The structure will in turn be analyzed in context of ligand-binding addressed in pharmacological assays commonly used in the laboratory.

APPLIED TECHNIQUES

Depending on the project level and duration, projects will entail:

  • Cell transfection or transduction with DNA or baculovirus particles (HEK293)
  • Protein expression (E. coli or HEK293)
  • Protein purification (affinity and size-exclusion chromatography)
  • Mammalian cell culture (HEK293)
  • Biochemical assays (in vitro) and analysis
  • Negative stain electron microscopy
  • Cryo-electron microscopy

WHAT THE AUTZEN LAB OFFERS YOU

We offer you great opportunities for personal and professional development, and an exciting and stimulating research project set in an inclusive, creative, fun, and international environment. We have access to a wide selection of state-of-the-art equipment for cellular, biochemical, and biophysical protein characterization.

Read more on our website: www.autzenlab.com

WHO ARE YOU?

We are looking for motivated candidates with an interest in biochemistry, structural biology, and/or pharmacology to join our team.

The project can be tailored to the BSc and MSc level and to a 3–6-month ERASMUS exchange.

Please state why you are interested in joining the lab, including how it fits into your career and educational goals. Please include a list of your completed courses.

Contact/Kontakt: Henriette E. Autzen, henriette.autzen@bio.ku.dk

Location/Sted: Section for Biomolecular Sciences, Linderstrøm-Lang Centre for

Protein Science / Sektion for Biomolekylære Videnskaber

Biocenter, Ole Maaløes Vej 5, 2200 København N

Keywords: Molekylærbiologi, molecular biology, kloning, cloning, proteinkemi, protein chemistry, biokemi, biochemistry, proteiner, proteins, membrane protein, membranprotein, structural biology, strukturbiologi, pharmacology, farmakologi, ERASMUS

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