by Lam Nguyen
In the human body, there are about 37 trillion cells. Each cell is made up of organelles that are busy creating proteins, digesting nutrients, and transporting different molecules or other organelles around. In order to facilitate the diverse functions different organelles assume, the plasma membrane, a barrier made up of proteins and lipids, helps compartmentalize different metabolic reactions to specific organelles and regions of the cell. Plasma membranes also play a critical role in the transportation of nutrients and signals between organelles through a process called fusion. A major topic within plasma membrane research, membrane fusion is a process in which two separate lipid membranes fuse into one single layer [1]. This process is essential in the creation of many organelles, such as the ER, a particular organelle that has fascinated Dr. James McNew, professor of biosciences, ever since he first came to Rice University.
Dr. McNew received his Bachelor’s of Science in Biochemistry from Texas A&M University, his Ph.D. in Pharmacology from UT Southwestern, and he completed his postdoctoral fellowship at the Memorial Sloan-Kettering Cancer Center. His interest in cellular biology and membrane fusion started with his graduate work while researching how the peroxisome, an organelle responsible for various metabolic processes such as detoxification and cellular signaling, worked. This particular lab experience helped him realize that he had a passion for understanding basic molecular biology and “how different cellular components moved around the cell.” His burgeoning interest in basic cell biology followed him to his postdoctoral fellowship where his research centered around how proteins were moved, targeted, and carried to the Golgi apparatus, an organelle that processes and sends out newly synthesized molecules. Dr. McNew’s passion for cell biology and membrane fusion has defined much of the work he has done here at Rice. His original research pertains to understanding membrane fusion in the endoplasmic reticulum (ER). The ER is a network of membranous tubules that is involved in protein and lipid synthesis1. Dr. McNew and Dr. Michael Stern, a fly geneticist and professor at Rice, observed how these tubules came together, but “the proteins involved were unclear.” They then hypothesized that the protein elastin, a protein present in connective tissue, played a significant role in ER membrane fusion. The two were able to confirm that elastin helps ER tubules come together, and they characterized the protein by studying it both in vivo (in a test tube) and back in fruit flies.
Dr. McNew also describes himself as a “basic cell biologist” and that his work is generally “far removed from something medicinal or therapeutic.” Work by clinicians on the elastin protein, however, has confirmed that elastin plays a role in physiological processes in humans. In fact, defects in the gene encoding for elastin play a role in hereditary splasic paraplegia (HSP), a group of genetic diseases where weakness and stiffness in the muscles gradually lead to muscular degeneration overtime. This discovery has allowed Dr. McNew to connect his basic biology research to clinical applications. Alongside characterizing the mechanism of elastin in ER membrane fusion, Dr. McNew has also been deepening his understanding of how mutations in this protein can cause human diseases.
Trying to understand how disruptions in the elastin and ER membrane fusion could cause the degeneration of muscles seen in HSP, Dr. McNew’s lab discovered that the loss of elastin function results in neurodegeneration which eventually leads to the deterioration of muscles. This explains how “people who have HSP lose motor control and their ability to walk.” Between adjacent neurons, small signaling molecules called neurotransmitters are transported to send the electrical signal from one neuron to another. Dr. McNew observed that defects in elastin seen in HSP patients are somehow connected to the lack of neurotransmission. The lab was initially puzzled because they saw signs of muscle degeneration but not neurodegeneration. “Even though nerve damage is a known cause of muscle atrophy, conventional wisdom is that the nerve cells die first," Dr. McNew explains. Consequently, Dr. McNew and his lab have begun investigating the cellular communication involved in this seeming paradox by learning about the other signalling molecules involved, specifically the torr kinase protein [2]. The McNew lab has been researching how the lack of neurotransmission is signalled by the torr kinase in order to provoke cell death in muscular tissue.
Dr. McNew plans on building on the vast amount of data that his lab has obtained by further exploring other types of proteins that work with elastin and torr. Understanding these biochemical interactions will allow scientists to have a better picture of how elastin defects, lack of neurotransmission, and muscular degeneration are all connected to each other. The opportunity to discover new conclusions and to be on the forefront of scientific innovations is what often inspires undergraduates to get involved in research. When asked about if he has any advice for aspiring undergraduate researchers, he says that one has to be “okay with failure.” “It is very exciting and engaging to do something for the very first time. The feeling that you are the first person to do something is very addictive and keeps you going!” exclaims Dr. McNew. It is this excitement that will continue to inspire Dr. McNew in furthering his understanding of our cells and how they work.
Works Cited
(1) Daumke, O.; Praefcke, G. Structural Insights Into Membrane Fusion At The Endoplasmic Reticulum. Proceedings of the National Academy of Sciences 2011, 108 (6), 2175-2176.
(2) Loewith, R.; Hall, M. Target Of Rapamycin (TOR) In Nutrient Signaling And Growth Control. Genetics 2011, 189 (4), 1177-1201.