Pharmacology

My group has three major lines of research:

1) To clarify the evolution of the mechanisms for long-term memory. The molecular machinery for memory formation constitutes one of the most challenging questions for neuroscientists to resolve. Such complex mechanisms can only be understood by studying their components. Our approach is to investigate how and when the genes and their proteins originated that are involved in these processes. We already know that most of them arose at the origin of the vertebrates more than 500 million years ago. We use the zebrafish to investigate their localization and functions.

1) To resolve the evolution of important gene families in vertebrates, particularly gene families expressed in the nervous system and in the endocrine system. The purpose is to discover at which point new functions have arisen and how functions have changed during evolution. We are primarily investigating gene families that include neuropeptides, G-protein-coupled receptors, ion channels, and genes involved in vision.

2) To characterize the NPY (neuropeptide Y) system of peptides and G-protein-coupled receptors involved in appetite regulation. Both genetic studies in humans and functional studies of the receptors from humans and other species help shed light on the complex regulation of hunger and satiety.

Many hundreds, perhaps thousands, of vertebrate gene families are now known to have expanded in two dramatic events that took place approximately 500 million years ago, namely two genome doublings or tetraploidizations (called 2R for two rounds of genome duplication). In addition, a third tetraploidization (3R) took place in the ancestor of teleost fishes. These events explain a great deal of the complexity of presently living vertebrates, and also explain functional overlap for members of many gene families. We are using a combination of phylogenetic sequence analyses and chromosome comparisons across species, to distinguish gene duplication events in gene families of special functional interest. This approach is very useful to identify corresponding genes (orthologues) in different species for comparisons of functions. The results have important implications for our ability to understand how functions arise, change, and occasionally even disappear during evolution. Among the gene families that we have studied, or are presently studying are the opioid peptides (enkephalins etc.) and their receptors, growth hormone and prolactin and their receptors, oxytocin-vasopressin receptors, somatostatin receptors, voltage-gated sodium and calcium channels, and receptors for the main neurotransmitters glutamate, acetylcholine, GABA, noradrenalin and serotonin.

NPY is one of the most abundant neuropeptides in the brain of all mammals, including humans. Together with its two related peptides PYY and PP, it regulates appetite, metabolism and numerous other physiological functions. We are especially interested in the NPY-family receptors that mediate hunger and satiety. We study both the genetic variation in the receptors among humans and the functional properties of the receptors in response to various pharmacological compounds.

Dan Larhammar

professor at Department of Neuroscience, Larhammar: Pharmacology

Email:
Dan.Larhammar[AT-sign]neuro.uu.se
Telephone:
+4618-471 4173
Mobile phone:
+46 70 6349214