 |
||||
Discovery in Malaria Research |
||||
|
January 20, 2012 New Malaria Discovery Published In Top Life Sciences Journal - CELL
(Left to right - Drs. Kasturi Haldar, Souvik Bhattacharjee, and Robert Stahelin) |
|||
Notre Dame researchers report fundamental malaria discovery A team of researchers led by Kasturi Haldar and Souvik Bhattacharjee of the University of Notre Dame's Center for Rare and Neglected Diseases has made a fundamental discovery in understanding how malaria parasites cause deadly disease. The researchers show how parasites target proteins to the surface of the red blood cell that enables sticking to and blocking blood vessels. Strategies that prevent this host-targeting process will block disease. The research findings appear in the Jan. 20 edition of the journal Cell, the leading journal in the life sciences. The study was supported by the National Institutes of Health. Malaria is a blood disease that kills nearly 1 million people each year. It is caused by a parasite that infects red cells in the blood. Once inside the cell, the parasite exports proteins beyond its own plasma membrane border into the blood cell. These proteins function as adhesins that help the infected red blood cells stick to the walls of blood vessels in the brain and cause cerebral malaria, a deadly form of the disease that kills over half a million children each year. In all cells, proteins are made in a specialized cell compartment called the endoplasmic reticulum (ER) from where they are delivered to other parts of the cell. Haldar and Bhattacharjee and collaborators Robert Stahelin at the Indiana University School of Medicine- South Bend (who also is an adjunct faculty member in Notre Dame's Department of Chemistry and Biochemistry), and David and Kaye Speicher at the University of Pennsylvania's Wistar Institute discovered that for host-targeted malaria proteins the very first step is binding to the lipid phosphatidylinositol 3-phosphate, PI(3)P, in the ER.
This was surprising for two reasons. Previous studies suggested an enzyme called Plasmepsin V that released the proteins into the ER was also the export mechanism. However, Haldar, Bhattacharjee and colleagues discovered that binding to PI(3)P lipid which occurs first is the gate keeper to control export and that export can occur without Plasmepsin V action. Further, in higher eukaryotic cells (such as in humans), the lipid PI(3)P is not usually found within the ER membrane but rather is exposed to the cellular cytoplasm. Haldar and Bhattacharjee are experts in malaria parasite biology and pathogenesis. Stahelin is an expert in PI(3)P lipid biology, and David and Kaye Speicher are experts in proteomics and a method called mass spectrometry. Their interdisciplinary collaboration reveals a fundamental, novel cellular function, whose disruption can provide new therapies that are urgently needed for malaria. Contact: Kasturi Haldar, khaldar@nd.edu
Originally published on ND Newswire by Pamela Tamez and William Gilroy |
||||
|
||||
Christmas Break & Marisa Truong's Mission Trip to Nicaragua |
||||
CRND Class Co-ordinator Marisa Truong went to Nicaragua on a mission trip over the Christmas break! Her team, "The Nicaragua Children's Health Initiative 2011" accompanied a physician and carried health supplies to people in several villages who do not have ready access to healthcare resources. The team assisted with preventive healthcare and education. Several of Marisa's team posted a blog about their trip with pictures of many new friends and events with the community. Please visit the Nicaragua Mission Trip blog. (Below, from the right - Marisa Truong, Sarah Lee, Julia Kang - blogger) |
||||
 |
||||
|
||||
CRND's 6th Class Graduates! |
||||
 |
||||
| December 2, 2011: The 6th Class in Developing Health Networks in Rare and Neglected Disease (BIOS60565) - Left to right:Natalie Bott, Aaron Patzwahl, Marisa Troung, Kasturi Haldar, Jennifer Van Trieste, Brianna McSorley, Michael Clark, Wei Lu, Will Wall. -- "This class developed the process by which trained undergraduate students could directly interact with patients and assist with obtaining patient medical records." - Professor K. Haldar (Photo, Wall, 2011)
|
||||
|
||||
Mr. Michael McLaughlin on Blepharophimosis |
||||
 |
||||
December 2, 2011- Mr. Michael McLaughlin, Senior Director of Regional Development at the University of Notre Dame and family members address Professor Kasturi Haldar's BIOS60565 class (Photo: Wall, 2011) Mike McLaughlin and members of his family visited with the CRND's class on Developing Health Networks in Rare and Neglected Diseases to teach students about Blepharophimosis and share their perspectives as a family with several members affected by this rare genetic condition. Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is inherited as an autosomal dominant pattern (50% chance of inheritance). It is characterized by a complex eyelid malformation: eyelids that are narrow horizontally (blepharophimosis), a skin fold (lower eyelid) on the sides of the nose (epicanthus inversus), and drooping of the upper eyelids (ptosis). Numerous corrective operations beginning in early childhood are required to attain proper vision and eyelid functionality. Mr. and Mrs. McLaughlin, both outgoing speakers brought an ample measure of good humor, which was shared by all the family, to narrating their multi-generational history. Mrs. Patty McLaughlin (also UND staff), who does not have BPES, has played a significant role in researching the condition and she related her journey of discovery to class. Mr. McLaughlin shared his experiences growing up with BPES (inherited from his father) and the kinds of choices he made to overcome many social and medical challenges. The resilience of the McLaughlin family in undergoing many surgeries was a compelling feature of the story and provided students with a window into the kinds of resources - medical, financial, emotional, and spiritual - required to ameliorate a rare disease. Mr. McLaughlin's surgeries occurred later in life and he remarked on the considerable difference these operations made on the way people naturally responded to him. Current medical advances have enabled surgery to begin correcting features of BPES much earlier (often between the ages of 3-5). The timing of surgeries is, of course, critical to outcomes in children. Throughout class, students joined in a relaxed Q&A with the very generous McLaughlin clan. As Mr. William Wall, class videographer summarized, "Mike and Patty are both gifted storytellers and gave the class an intimate and honest view of a rare disease's impact on a family." The visit of the McLaughlin family to CRND is deeply appreciated.
|
||||
|
|
|||
Dr. Michael Pfrender on Genomics & Rare Diseases
Professor Michael Pfrender, Director of the Genomics Core in UND's Department of Biology has a broad set of interests in evolutionary and ecological genomics, particularly adaptations in natural populations that are responsive to changing environments. Recently, Dr. Pfrender shared his interests in Genomic Medicine and rare diseases with CRND students. Program Coordinator, Ms. Marisa Truong summarized the points of emphasis: "the implications of high throughput sequencing to rare diseases and the issues surrounding too much data." Yes, that can be a problem!
High-Throughput Screening is a mode of experimentation that allows researchers to conduct millions of genetic tests rapidly and relatively inexpensively in order to map out the dynamic relationships among the gene functions and their products. The interactive bio-networks or biological pathways illuminated by high-throughput screening are vital to modeling disease processes as systems. While a few diseases are the result of singular genetic mutations, most are a consequence of multiple genetic variables interacting over time within changing environments. Additionally, some genes influence the development of more than one disease.
Dr. Pfrender referenced an article in the New York Times, "Redefining Disease, Genes and All," and pointed to its excellent illustration of gene clusters associated with various diseases.** Proportionate visual mapping illustrates the number of genes associated with particular disorders in a way that makes the relationships among elements of very large datasets more easily comprehensible. Dr. Pfrender also talked with students about the importance of databases, computational processing and the ability to take innovative and diverse approaches to the same problems - for example, combining the results of multiple molecular studies and performing computational analyses to generate new questions and findings from the original data.
Dr. Pfrender conveyed to students the kinds of questions new technologies allow us to ask about the evolution of the genome and its responses to accumulations of environmental stress over time. He introduced the concept of "fitness" as the body's ability to maintain "phenotypic plasticity and adaptive evolution." In his explanation of the interaction between disease progression and a changing genomic environment, Dr. Pfrender helped students understand that there are multiple points along the way where the body's evolutionary ability to adapt may be favorably aided. Finding these points is crucial.
In addition to explaining the potential benefits of utilizing the tools of genomic medicine, Dr. Pfrender also recalled the film Gattaca and discussed the ethical considerations that must be addressed in preventing social harm and discrimination based on genetic profiles. Science is close to catching up to science fiction in terms of technological capability and it is essential that safeguards be maintained to ensure the application of these technologies for the benefit of society and the cure of diseases.
With the advent of new technologies and methods discussed by Dr. Pfrender, the cost of experimentation is changing beneficially in the direction of helping diseases previously orphaned by the unmanageable costs of experimentation for relatively small patient populations. CRND thanks Dr. Pfrender for sharing his expertise, passion and enthusiasm for the potential breakthroughs in rare diseases, which are now on the horizon.
**Note! The source of the New York Times illustration was an article and set of figures published by members of the University of Notre Dame Center for Complex Network Research and Department of Physics. Link to the original article and source maps at :Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabási AL. "The human disease network". Proceedings of the National Academy of Science U S A. 2007 May 22;104(21):8685-90
PLoS One Publishes CRND Course Article: 'Defining Natural Hisory'
October 2011 - The 64 student authors of an article describing their participation in the CRND collaboration with the NIH's Natural History Study for NP-C Disease are pleased to announce that PLoS One has published their article, "Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C."
Link to: The Publication Announcement |
Link to PLoS One and download : "Defining Natural History...'" |
|
|
|||
CRNDNewsletter- SIGNAL - 2nd Issue
Current issue of SIGNAL reports on: CRND's activities for the 10th annual Rare Disease Month, including the lectures of several NP-C disease speakers; the visit of President and Mrs. Koehler to discuss international rare disease collaborations; the publication in PLoS One of the undergraduate classes' natural history of NP-C article; a brief report on the Schorey group's work on utilizing exosomes in TB diagnostic and vaccine development; announcements of recent awards; and a spotlight article on Dr. Patricia Champion's work on the ESX "biological machine." The current edition of SIGNAL is available for download on the left sidebar or here
About The Center for Rare and Neglected Diseases
Science for Society
Around the globe, people are suffering and dying from diseases that have generally been ignored by major pharmaceutical companies because the potential financial rewards for developing new drugs and vaccines to treat them are insignificant. These are the rare and neglected diseases of the world. There are thousands of rare diseases, typically defined as those, which afflict less than 200,000. Among them are cystic fibrosis, thalassemia, Niemann-Pick C disease, and several of the rare forms of cancer. Neglected diseases, by contrast, can affect billions, but like their rare counterparts, have been ignored by researchers. This is especially prevalent in the developing world and in pockets of grinding poverty in developed nations, where the populations suffering from illnesses such as tuberculosis, malaria, and lymphatic filariasis do not have the money to buy drugs and vaccines, giving pharmaceutical companies little incentive to develop treatments that cost far more than could ever be recouped through reasonable prescription prices. The result is a gaping hole in healthcare—one which Notre Dame is uniquely positioned to fill.
Rare Diseases: those which afflict less than 200,000. Examples are cystic fibrosis, thalassemia, Niemann-Pick Type C Disease, adrenolekodistrophy and several forms of cancer.
Neglected Diseases: diseases of poverty, lymphatic filariasis disease pathologies of TB and Malaria.
Where We Are:
University of Notre Dame
Center for Rare and Neglected Diseases
Galvin Life Science Building
Notre Dame, IN 46556
Email at: crnd@nd.edu
Phone (574) 631-3372
Fax (574) 631-9788
