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 T1R3 homodimer functions as a glucose-sensing receptor and is involved in glucose-induced insulin secretion in pancreatic β-cells and energy homeostasis governed by the brain. Modulation of T1R3 with cyclic peptides has vast applications ranging from the design of new sweeteners to a more general tool for understanding the molecular mechanisms of how we perceive sweets.

In this project you will express and purify the glucose-sensing receptor, reconstitute it into nanodiscs, and subject it to de novo cyclic peptide screening. You will perform pharmacological assays on cultured, mammalian cells transiently expressing T1R3 and heterotrimeric G protein complexes to determine how the cyclic peptides work. Identification of novel cyclic peptide binding partners will in turn be analyzed via a spectrum of techniques 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