Research Location: University of British Columbia - Point Grey

Microsporidia are a group of parasites that infect animals and immunocompromised humans. In infected individuals, they cause severe diseases, like encephalitis (inflammation of the brain) and gastroenteritis (inflammation of the stomach). As organisms that are dependent upon their host for survival, some of the microsporidia’s organelles (internal structures) and metabolic functions are missing or deficient in comparison to other single-celled organisms. One example is the mitochondrion, an organelle that normally contains many enzymes important for cell metabolism, including those responsible for the conversion of sugar to usable energy. A highly reduced relic of the mitochondrion was recently discovered in microsporidia. The role and metabolic function of this deficient organelle remain unclear. Dr. Lena Burri’s research project is to identify and characterize proteins that are imported into the mitochondrion, how these proteins are directed to their final destination and in which metabolic pathway they are involved. Understanding the function of the relic mitochondria in microsporidia may provide ways to combat these organisms, as mitochondrial functions are important potential drug targets.

Although they severely affect the lives of millions of individuals, Restless Leg Syndrome (RLS) and rapid eye movement behavior disorder (RBD) are two sleep disorders that are not commonly diagnosed. Unlike more common conditions like sleepwalking, RLS and RBD movements occur during REM sleep or natural active sleep (AS), which are usually characterized by a state of atonia, or sleep paralysis. During AS, sensory transmissions to the brain are reduced; spinal inhibitory interneurons (neurons confined wholly within the spinal cord) are thought to underlie this reduction. However, virtually nothing is known on how these spinal interneurons are regulated. Dr. Yanshen Deng is investigating how the activity of certain spinal interneurons change as a consequence of alterations in behavioural state e.g. wakefulness vs. sleep. She is researching how these spinal interneurons are triggered to inhibit specific spinal sensory channels, and whether such interneurons are facilitated during AS. Yanshen’s research aims to advance basic sleep and spinal cord science and may help advancement of knowledge in sleep-related sensorimotor disorders such as RLS and RBD and pain following spinal cord injury.

Seizures are more common during an infant’s first month than at any other time during their development. They are caused by temporary abnormal electrical activity in the brain and can have long-lasting consequences such as memory impairments and an increased risk for epilepsy. Unfortunately, anticonvulsant treatments are ineffective for at least 35% of babies who have seizures as newborns. Currently, the mechanisms underlying the onset of these seizures are unclear. While research indicates that increased transmission of glutamate (a neurotransmitter) may result in seizures in the adult brain, there have been indications that seizures in newborns may be triggered by a reduction in glutamate transmission. These and other findings suggest that certain glutamate receptors may have different roles in causing seizures over the course of neurological development. Dr. John Howland is investigating the role of glutamatergic transmission levels and seizures during the neonatal period. He is analyzing two highly specific glutamate receptor antagonists (blockers) to determine the specific receptor subtypes involved in triggering seizures. Results from his research may have significant implications for the understanding of neonatal seizures and the development of novel drug targets for their prevention and treatment.

The majority of therapeutic drugs now in use are “so-called” small molecules – compounds that exert their desirable effect by interrupting or otherwise interfering with an abnormal physiological process. More recently, a new class of protein-based drugs has been developed, including various growth factors and Epoetin. Most protein-based drugs have sugars attached to their surface that are known as glycoproteins. These sugars play a role in directing the drug to its site of action and maintaining the protein in the bloodstream. If enzymes in a patient’s body cut or cleave the sugar molecules from the protein, the drug is cleared from the body. If scientists could produce more stable forms of glycoproteins, the drugs would remain in the bloodstream, reducing and potentially eliminating the need and costs of frequent doses. Using newly developed methodologies created in the laboratory of his supervisor Dr. Stephen Withers, Dr. Young-Wan Kim is working to address this issue by engineering new enzymes that would attach sugars via a sulfur atom and allow, for the first time, the generation of stable versions of these therapeutic proteins.

All animals are colonized by a large number of non disease-causing microorganisms, referred to as the normal microbiota. Sites colonized by these microorganisms include the skin and the genital tracts, with the most heavily colonized site being the large intestine. The intestinal microbiota carries out important roles in a variety of areas, such as absorption of nutrients and prevention of infectious disease. Dr. Claudia Lupp is investigating the importance of the intestinal microbiota in diarrheal disease caused by enteropathogenic Escherichia coli (E. coli). Enteropathogenic E. coli include the human pathogens enterohemorrhagic and enteropathogenic E. coli (EHEC and EPEC), which cause significant illness and death around the world. She will use the closely related mouse pathogen Citrobacter rodentium as an experimental model to determine the effects of diarrheal disease on the normal microbiota and to investigate how the microbiota might be manipulated in order to prevent disease. Understanding the body’s innate defenses against infectious disease, including those provided by the normal microbiota, is important for health maintenance. This information ultimately may be used for strategies to prevent and to cure infectious disease by bolstering the body’s natural defenses.

Traumatic injuries to the nervous system, such as spinal cord injury, can exert enormous physical, psychological, emotional and financial costs to the individual, their families and to society. A major physical consequence of spinal cord injury is sensory dysfunction (loss of normal sensory functions, including touch, pain, and temperature, and an inability to perform accurate motor tasks). All too often, this loss of sensory function is permanent, as spinal sensory nerves fail to regenerate after injury. There are many molecules within the nervous system that are capable of inhibiting the regeneration of nerve fibres. However, the exact mechanisms responsible for halting regrowth of sensory nerve fibres into the spinal cord after injury remain undefined. Dr. Lowell McPhail’s research objective is to identify and overcome the barriers to sensory fibre regeneration, following both acute and chronic dorsal root injury. Specifically, Dr. McPhail is examining injuries at the dorsal root entry zone (the point at which sensory axons enter the spinal cord), as it serves as an excellent system to model the environment of regenerating axons bridging the spinal cord injury site. Dr. McPhail is also investigating the mechanisms responsible for the ability of spared or uninjured sensory neurons to partially compensate for the lost sensory input following dorsal root injury. His research will attempt to identify potential therapeutic strategies for neurotrauma including, sensory nerve injuries, spinal cord injury and brain injuries.