Why Typhoid Fever Is Human Specific: Dr. Ajit Varki and Coworkers Discover One Explanation

Typhoid Mary, Not Typhoid Mouse: Lack of enzyme explains why typhoid fever is a human-specific disease

The bacterium Salmonella Typhi causes typhoid fever in humans, but leaves other mammals unaffected.  Researchers at University of California, San Diego and Yale University Schools of Medicine now offer one explanation — CMAH, an enzyme that humans lack. Without this enzyme, a toxin deployed by the bacteria is much better able to bind and enter human cells, making us sick. The study is published in the Dec. 4 issue of Cell.

In most mammals (including our closest evolutionary cousins, the great apes), the CMAH enzyme reconfigures the sugar molecules found on these animals’ cell surfaces into a form that the typhoid toxin cannot bind. Humans don’t produce CMAH, meaning our cell surface sugars are left unchanged — and as this study shows, in a state just right for typhoid toxin attachment.

“We started this project looking at something completely different in relation to cancer, but serendipity instead helped us solve the mystery of what the typhoid toxin binds,” said co-senior author Ajit Varki, MD, Distinguished Professor in the Departments of Medicine and Cellular and Molecular Medicine at UC San Diego. “That’s the beauty of basic research — though we didn’t set out with the intent, these findings may now spur the development of new therapies for typhoid fever.” Varki co-directed the study with Jorge E. Galán, PhD, DVM, professor and department chair at Yale University School of Medicine. … Read the full story from the UC San Diego Newsroom

UC San Diego-Human Longevity Inc. Agreement Seeks to Accelerate Medical Science

Thousands of patient genomes expected to fuel diverse medical research, beginning with cancer

The new collaborative research agreement between Human Longevity Inc. (HLI) and the University of California, San Diego, announced today, represents a significant and necessary step in efforts to research and translate the potential of the human genome into novel and real treatments and therapies able to change and improve the human condition.

“This agreement brings together the resources of two entities that, in combination, may ultimately help improve countless lives,” said David A. Brenner, MD, vice chancellor of health sciences at UC San Diego and dean of the UC San Diego School of Medicine. “HLI aims to bring leading-edge thinking in genomics technologies. UC San Diego boasts some of the world’s finest researchers and physicians working at places like the Moores Cancer Center. Together, we will collaborate to marshal the people, the tools and the resources to really make a difference in human health.” … Read the full story from the UC San Diego News Center

Toward a New Model of the Cell

Everything You Always Wanted to Know About Genes

Turning vast amounts of genomic data into meaningful information about the cell is the great challenge of bioinformatics, with major implications for human biology and medicine. Researchers at the University of California, San Diego School of Medicine and colleagues have proposed a new method that creates a computational model of the cell from large networks of gene and protein interactions, discovering how genes and proteins connect to form higher-level cellular machinery. …Read the full story from the UCSD Newsroom


Trey Ideker, PhDThe new approach comes from the medical genetics laboratory of Trey Ideker, PhD, in the departments of bioengineering and medicine. Postdoctoral fellow Janusz Dutkowski, PhD, is lead author and Michael Kramer, PhD, a coauthor of the study report in Nature Biotechnology.

Ideker, senior author, is professor of bioengineering and medicine and chief of the Division of Medical Genetics in the Department of Medicine.

Citation for the report:  Dutkowski J, Kramer M, Surma MA, Balakrishnan R, Cherry JM, Krogan NJ, Ideker T. A gene ontology inferred from molecular networks. Nature Biotechnology (2012) doi:10.1038/nbt.2463. Published online 16 December 2012  Read the abstract

Biomarking Time

Methylome modifications offer new measure of our “biological” age

Women live longer than men. Individuals can appear or feel years younger – or older – than their chronological age. Diseases can affect our aging process. When it comes to biology, our clocks clearly tick differently.

In a new study, researchers at the University of California, San Diego School of Medicine, with colleagues elsewhere, describe markers and a model that quantify how aging occurs at the level of genes and molecules, providing not just a more precise way to determine how old someone is, but also perhaps anticipate or treat ailments and diseases that come with the passage of time. … Read the full story from the UCSD Newsroom


Trey Ideker, PhDTrey Ideker, PhD, is co-senior author of the study report. He is professor of medicine and chief of the Division of Medical Genetics, professor of bioengineering and faculty investigator in the UCSD Institute for Genomic Medicine.The overall goal of Ideker’s work is to map and model molecular networks of cellular processes in health and disease, particularly in cancer and the response to genotoxic stress.

Coauthors of the study report include Rob DeConde, a graduate student in Ideker’s laboratory.

Read the abstract of the study report in PubMed

Citation: Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan J-B, Gao Y, Deconde R, Chen M, Rajapakse I, Friend S, Ideker T, Zhang K: Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Molecular cell doi:10.1016/j.molcel.2012.10.016. PMID: 23177740

How Infectious Disease May Have Shaped Human Origins

Inactivation of two genes may have allowed escape from bacterial pathogens, researchers say

Roughly 100,000 years ago, human evolution reached a mysterious bottleneck: Our ancestors had been reduced to perhaps five to ten thousand individuals living in Africa. In time, “behaviorally modern” humans would emerge from this population, expanding dramatically in both number and range, and replacing all other co-existing evolutionary cousins, such as the Neanderthals. … Read the full story from the UCSD Newsroom

Sexual Selection by Sugar Molecule Helped Determine Human Origins

Researchers at the University of California, San Diego School of Medicine say that losing the ability to make a particular kind of sugar molecule boosted disease protection in early hominids, and may have directed the evolutionary emergence of our ancestors, the genus Homo….Read the full story from the UCSD Newsroom

Dr. Ajit Varki

Dr. Ajit Varki, pictured above left, is senior author along with Dr. Pascal Gagneux, who is professor in the Department of Cellular and Molecular Medicine. Ajit Varki, MD, is Distinguished Professor of Medicine and Cellular and Molecular Medicine, Co-Director of the Glycobiology Research and Training Center, and Co-Director of the UCSD/Salk Center for Academic Research and Training in Anthropogeny.   |  Read the study published in PNAS (free full text)