Mechanisms of attention: implications for brain and behavior

Our attention can be shifted automatically in response to sudden events, such as a hand being raised in a classroom, or can be allocated voluntarily in response to our internal goals and expectations, such as looking left or right before crossing a street. Dysfunction of either type of attentional process may be expressed in a variety of disorders, such as schizophrenia, Parkinson’s disease, autism, and attention deficit disorder. Currently, diagnosis and rehabilitation of attention in patients relies on behavioral procedures that were established more than 20 years ago. Jelena Ristic’s recent research, conducted with both children and adults, suggests that these traditional procedures are based on flawed theoretical assumptions and as such, they do not reflect the main properties of human attention. She is currently working towards developing novel behavioral, as well as imaging, methodologies that will capture accurately the key properties of human attention. Results from her basic research will be used to develop more effective diagnostic techniques and rehabilitation programs for patients with attention dysfunctions.

Caenorhabditis elegans dog-1 gene mechanism in genome stability

Genes that contribute to normal cell reproduction, growth and DNA repair are essential for healthy cell function in all organisms. The dog-1 gene plays a role in maintaining the stability of the genome of Caenorhabditis elegans, a tiny worm frequently studied by researchers because it has many molecular characteristics that are central to human biology. However, little is known about how the dog-1 gene functions to maintain genome stability. Jillian Youds is studying how this gene functions in the cell to gain a better understanding of how it contributes to DNA sequence stability. Given that mutations in the genes required for stability are often underlying causes of disease, this research could provide further understanding of the development of cancer.

Functional characterization of Bardet-Biedl proteins

Bardet-Biedl Syndrome (BBS) is a complex genetic disease that affects many different body parts, including the eyes, kidney and heart. Symptoms include blindness, obesity, diabetes, kidney dysfunction, congenital heart defects and extra fingers or toes. At least eight genes (BBS1 to BBS8) are linked to the syndrome. Recent studies suggest that defective cilia (short, hair-like projections that protrude from the cell surface and help clean out airways) may be the primary cause of the syndrome. Junchul Kim is investigating whether this defect causes Bardet-Biedl Syndrome. He is studying the role of proteins encoded by BBS genes to see if mutations in these genes affect different body parts during development. This research could provide insights into how the syndrome develops and potentially lead to new treatments for many common disorders, such as diabetes and obesity.

The role of a novel gene involved in autophagic programmed cell death

All multi-cellular organisms begin as a single cell that multiplies and develops into a fully formed adult. While millions of cells are produced during development, the process of programmed cell death (apoptosis) removes obsolete cells. Errors in this process can cause neurodegenerative disorders and cancers. Suganthi Chittaranjan aims to identify the genes that control cell death. Using powerful tools available at Canada’s Michael Smith Genome Sciences Centre, Suganthi has identified 500 genes that are activated before cells die. One gene in particular may play a role in both programmed cell death and the immune system’s defensive response. If the research succeeds in identifying a common gene that controls both processes, the gene could be used as a target in developing therapy for controlling cancer and improving the immune system of cancer patients.

Competition for control of behavior

Behavioural responses are influenced by information from a person’s immediate environment and an individual’s goals and intentions. Conflict between these sources occurs regularly, and is particularly evident in eye movements, in which split-second decisions about where to look next are made more than 100 times a minute. Many neurological and psychiatric disorders such as schizophrenia, Parkinson’s disease, Alzheimer’s, depression and anxiety are characterized by inefficient or inappropriate eye movements and other behaviours. Amelia Hunt is studying the physiology of eye movements to assess how conflicts between intentions and sensory responses are resolved. She is also investigating whether models of eye movement control can apply to other complex behaviours and disorders. The research could inform and guide intervention strategies to be used when behavioural controls begin to break down from illness or trauma.

The role of the PI3K pathway in embryonic stem cell proliferation and differentiation

Embryonic stem (ES) cells have the ability to differentiate into any cell type, such as skin, muscle or nerve cells. Differentiated ES cells potentially could be used to replace damaged tissues. However, undifferentiated EC cells form benign tumours following transplantation, thus ES cells must first properly differentiate into the desired cell type. Frann Antignano is investigating what causes ES cells to either self-renew or differentiate. The long version of a protein called SHIP plays a role in differentiation, while a shorter version called sSHIP is found in undifferentiated cells. Frann is examining the role of sSHIP in ES cell renewal by reducing the protein’s levels to see if that leads to increased self-renewal. Results from the research could lead to therapies for controlling ES cell differentiation to treat a variety of conditions, including Parkinson’s disease.

Computer-assisted femoral head resurfacing

Every year more than 20,000 Canadians with advanced osteoarthritis receive hip replacements. A new surgical technique resurfaces the head of the femur (the long thigh bone between the hip and knee) with a metal cap, removing far less bone than the traditional method, which involves removing a large portion of the upper femur. Hip replacements for active patients under the age of 55 have significantly increased and many of these patients will likely outlive their first hip implants. This new technique will help ensure they have enough bone to support a second surgery. Surgeons use a cumbersome alignment guide to insert a wire in the top of the femur and position the implant, which leads to variations in alignment that can loosen the implant or cause the femur to fracture. Jill Brimacombe is designing a computer-assisted surgical technique to help surgeons position the implants more accurately. The computer-assisted tool could reduce surgery time, be easier for surgeons to use, and improve accuracy, which would lengthen the life span of patients’ implants.

Acid extrusion from rat hippocampal neurons; the potential role of a voltage-gated proton conductance

Intracellular pH, the amount of acid inside neurons (brain cells) changes during normal cellular activity and with conditions such as stroke. Left unregulated, these changes can alter brain cell function and contribute to their death following a stroke. Consequently, cells have developed mechanisms to maintain their intracellular pH within normal limits. The hippocampus, a part of the brain associated with learning and memory, contains some cells that are very susceptible and some that are very resistant to stroke-related cell death. Research has identified three mechanisms that regulate pH in hippocampal brain cells, but recent evidence suggests that these mechanisms are inhibited during a stroke. May Cheng is investigating whether there is a fourth mechanism, a voltage-gated proton conductance, that regulates pH by discharging detrimental acid from these cells. Identifying this additional mechanism could lead to new strategies to prevent or limit brain cell death following a stroke.

Host resistance and Salmonella Typhimurium Gastroenteritis

Salmonella species cause a variety of diseases, including diarrheal and systemic illness, signicificant causes of morbidity and mortality in the developing and developed world. To cause disease in healthy people, bacteria such as Salmonella typhimurium must first breach physical barriers, such as the mucous membrane lining internal organs, and then successfully avoid detection and destruction by the immune system. Gastroenteritis (inflammation of the stomach and intestine) in healthy humans and systemic illness in people with compromised immune systems result from the successful evasion of Salmonella typhimurium. Resistance to infection depends on a wide array of immune factors. Bryan Coburn is researching the role of host resistance factors and also the response of bacteria to these defenses in Salmonella-induced gastroenteritis. The research will potentially provide important insights about the mechanisms that influence susceptibility or resistance to Salmonella-induced gastroenteritis.

Prospective memory in obsessive compulsive disorder

People with obsessive compulsive disorder (OCD) experience persistent and distressing thoughts. In most cases, anxiety is relieved by performing repetitive acts, such as washing, checking or counting. Obsessive thoughts and compulsive behaviours can occupy so much time that people with OCD have difficulty functioning at work, taking care of themselves and relating to others. At its most extreme, OCD requires hospitalization. Carrie Cuttler is investigating whether impaired prospective memory — the type of memory required to remember an intention such as turning off the stove or taking medications — is linked to compulsive checking. Studies have shown prospective memory is impaired in patients with schizophrenia and depression, but little is known about the influence of anxiety on this type of memory. Carrie’s research could lead to more effective behavioural interventions that reduce the frequency of compulsive checking and improve quality of life for OCD patients.