Dr. Max D. Summers

Distinguished Professor
Endowed Chair in Agricultural Biotechnology
Texas A&M University
2475 TAMU
College Station, TX 77843-2475
(979) 847-9036
(979) 845-6305 Fax



Departmental Affiliations

Honors, Awards and Recognition





Dr. Max D. Summers is a Distinguished Professor and Holder of the Endowed Chair, in Agricultural Biotechnology at Texas A&M University. He received an A.B. degree in biology in 1962 from Wilmington College and a PhD in entomology from Purdue University in 1968. Summers was an assistant and an associate professor of botany at the University of Texas before moving to Texas A&M as a professor of entomology.

He is a member of the National Academy of Sciences, a Fellow in the American Academy of Microbiology and a Fellow of the American Association for the Advancement of Science. He was president of the American Society for Virology, chair of Class VI of the National Academy of Sciences. The Houston Intellectual Property Law Association honored him in 1999 as Inventor of the Year. He has authored or co-authored more than 150 publications and was listed in the top 250 (in the world) Most Highly Cited Authors in Microbiology by the Institute for Scientific Information. He is also a member of the Entomological Society of American Foundation Board of Councilors, and the Texas Academy of Sciences, Engineering and Medicine.
Dr. Summers was the editor of Virology, and executive editor of Protein Expression and Purification. He was a Foundation for Microbiology Lecturer of the American Society for Microbiology. He received the first Distinguished Alumni Award from the Purdue University School of Agriculture in 1992.

He has served on the U.S. Department of Commerce Biotechnology Technical Advisory Committee, the National Academy of Sciences Council of the Government-University-Industry Research Roundtable, and the Chiron Corporation Biotechnology Research Award Nominating Committee. He was a panelist of the Accountability and Federally Funded Research Panel, a sub committee of the Committee on Science, Engineering and Public Policy on Government Performance and Results Act.

Research contributions: 

Baculovirus Expression Vector System  
Dr. Max D. Summers’ research emphasis is molecular biology of virion maturation in the nucleus of cells. At the time the Baculovirus Expression Vector System (BEVS) was developed, bacterial and yeast expression vectors were available and both had demonstrated success with a number of proteins. However, both of these systems had significant shortcomings when they were used to produce structurally complex, biologically active proteins. Thus, there was a compelling need to augment the existing expression systems with a system that could produce proteins with properties more like those produced in mammalian cells. The need dictated the development of a system that would consistently produce proteins with authentic biological activity with relative ease, at low cost, and at a scale that would allow protein purification and detailed analysis.
As is often the case in biology, an alternative approach was developed to solve this problem from research that was distant from the mainstream approaches being used to develop expression vectors. While Max Summers and his graduate student Gale Smith, were working on the molecular biology of the family of insect viruses, Baculoviridae, they recognized that one gene was expressed at extremely high levels. They initiated studies to understand the essential elements of the promoter and the locus within the viral genome. These studies resulted in the knowledge that the gene was non-essential, and the strength of the promoter could be exploited for foreign gene expression. As part of the early assessments of safety for the baculoviruses, they also knew that this virus was non-toxic, did not replicate in mammalian cells and that the design and development of such an insect virus based vector system would have significant safety advantages over other vector systems. He and Gale proceeded to use these insights to develop the BEVS.
The Baculovirus Expression Vector System: The BEVS provides efficient, low cost, large-scale production of functionally active proteins. It fills many of the needs dictated by modern biological research. To date, well over a thousand proteins have been expressed using the BEVS, with 98% reported as biologically active. The BEVS then represents a breakthrough technology that is facilitating current high-throughput proteomic studies. The current explosion of knowledge of genomes and by extension the entire protein complement of an organism, is allowing the development of a series of new experimental tools. These are designed to facilitate understanding of biological systems at an unprecedented rate. One of these tools is the cloning of every gene encoded by an organism into a series of base vectors that can be purchased by scientists for rapid experimental development. The BEVS vectors are one of a small group of vectors that are being used for the development of these tools.
The ability to generate large quantities of functionally authentic proteins has opened many possible avenues for biological research. One such example is demonstrated with membrane proteins, many of which are receptors and primary targets for disease and modern medical intervention strategies. If a normal cell has one hundred copies of a protein receptor residing on the cell surface, it is not unusual for insect cell with a copy of the BEVS expressed gene, to have 5,000 to 20,000 copies of functional protein residing at the surface. This now facilitates the ability to assay its’ activity and make comparison of function after exposure to a spectrum of possible intervention agents. The BEVS is also being used to produce protein for three-dimensional structure analysis. Such knowledge provides for the precise design of intervention agents. The ability to use BEVS as a source for protein crystals, and large-scale drug testing, make the BEVS an important tool for drug discovery.
Another advantage of the BEVS is that the system not only can accept large genes, but more than one gene can be expressed. In this manner, proteins known to work in complexes can simultaneously be expressed to generate active, functional complexes. The ability to simultaneously express multiple genes has resulted in the understanding of complex structures. One example is the ability to generate secreted and active recombinant antibodies using BEVS. A second example has additional implications for the use of BEVS. All of the structural proteins of bluetongue virus have been simultaneously expressed using BEVS and this expression results in correctly assembled capsids. A similar result has also been generated using BEVS to assemble empty capsids of herpes simplex virus. Six viral genes assemble to generate a herpes virus capsid, and by using viruses containing all or combinations of these genes, the essential features of capsid formation was determined. These studies not only revealed basic biology of virus structure and assembly, but by removing the associated viral RNA or DNA, a system is developed that shows great potential to produce safe and clean vaccines.
The potential of BEVS to rapidly develop a candidate human vaccine has already been demonstrated. The Hong Kong ‘bird-flu’ virus (HSN1) developed the ability to spread directly from chickens to human. The virus was so deadly to chickens that the Hong Kong chicken industry was devastated with mass poultry eliminations. Farm workers and those involved in intervention programs were placed at significant risk of contracting the disease. To assure the safety of the workers, NIH requested the development of a vaccine. Protein Sciences, a company specializing in the use of the BEVS technology, delivered 1700 doses of an experimental vaccine within eight weeks. This included the time to identify, sequence and clone the gene responsible for the flu symptoms. The vaccine was a success. Only in science fiction can a vaccine be developed faster.

The BEVS represents a core technology that has greatly facilitated the understanding of many proteins from many organisms. These studies have broad applications and impact in basic research and practical medical applications for both humans and animals. The importance and broad acceptance of the BEVS technology is reflected in its acceptance in both the academic community and private sector. The broad recognition and acceptance by the scientific community is reflected in the determination by The Institute of Scientific Information (ISI) that Dr. Summers is one of the top 250 most highly cited microbiologists in the world. Acceptance of the BEVS by the private sector is reflected by the commercial licenses worldwide that are held for the BEVS technology (currently >70). Thousands of laboratories currently use the BEVS technology in their research programs. The BEVS represents a core technology that has greatly facilitated the understanding of many proteins from many organisms. These studies have broad applications and impact in basic research and practical medical applications for both humans and animals.

Sorting of Integral Membrane Proteins to Nuclear Membranes
Our research addresses the mechanism(s) of integral membrane protein sorting and trafficking to the eukaryote cell inner nuclear membrane, and to viral-induced intranuclear membranes. This is important because mutations in a number of inner nuclear membrane proteins correlate with several human diseases including muscular and lipid dystrophies. In eukaryotes, the nucleus is delimited by the nuclear envelope (NE), which consists of an outer nuclear membrane (ONM) and an inner nuclear membrane (INM) separated by a lumen, and penetrated by nuclear pore complexes. The current model for protein sorting to the INM states that integral proteins diffuse between the continuous membrane of the endoplasmic reticulum (ER) and the membranes of the NE, and are selectively retained at the INM by binding with nuclear factors such as protein or DNA.
We study the sorting of baculovirus envelope proteins that transit from their site of insertion in the ER, to the ONM and INM. These finally target to viral induced vesicle precursors which to form in the nucleoplasm and become the viral envelope. To identify potential regulatory and/or sorting factors that function during viral infection, several virus envelope proteins were studied for interactions with translocon proteins during integration. We show by comparing photocrosslinking of viral and INM cellular proteins through the translocon, that both viral and cellular transmembrane sequences (TMSs) occupy a similar location in the translocon, yet occupy different sites than do non-INM directed TMSs. These results provide evidence that: 1) INM directed TMSs are initially recognized and sorted at the translocon (a proposed new role for ER translocons); and, 2) for some integral membrane proteins, sorting to the nucleus may be an active process involving specific non-nuclear proteins [Saksena et al. (2004) PNAS 101:12537].
Our studies also demonstrate that sorting of a viral envelope protein to the INM is mediated by a specific INM-sorting motif (INM-SM). The INM-SM consists of the 33 N-terminal amino acids which contain a TMS and associated charges resulting in a specific orientation within the membrane [Braunagel et al. (2004) PNAS 1001:8372-8377]. Using site-specific crosslinking it was demonstrated following ER membrane integration, that the INM-SM is adjacent to two viral proteins; and the deletion of one of these proteins results in inefficient sorting of an integral membrane viral protein to nuclear membranes. With the observation that viral proteins may specifically facilitate viral envelope protein sorting to nuclear membranes, we speculate that in normal cells specific cellular proteins may function to facilitate sorting and trafficking. Using similar crosslinking experiments with the same INM-SM integration intermediates, we are testing for INM-SM proximity to cellular proteins that may facilitate the sorting of integral proteins in transit to the INM. Our studies now provide evidence that the co-translational integration and sorting of viral envelope proteins is a protein-facilitated and protein-regulated multistep process which may also be utilized during sorting of cellular INM directed proteins. Check our 2004 publications for details.