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Erin McCarthy selected as the recipient of the 2018 Richard L. and Norma L. McCarl Scholarship

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November 16, 2018 - Erin McCarthy, a graduate student in the Biochemistry, Microbiology and Molecular Biology (BMMB) Program, has recently been named the recipient of the Richard L. and Norma L. McCarl Scholarship.  She is originally from Erie Pennsylvania and came to Penn State in 2014 after earning her Bachelor of Science Degree from Mercyhurst University.

 

Richard McCarl was a professor emeritus of the Biochemistry and Molecular Biology Department having joined the Penn State Faculty in 1961 as an Assistant Professor.  Prior to coming to Penn State, he was a science teacher at Cochranton High School and Dayton Junior High School between 1950 and 1955 and also served his country in the Navy from 1945 to 1946, where he continued his service in the Naval Reserves until 1958.  During his tenure at Penn State, McCarl's research interests included lipid and carbohydrate metabolism in cell and tissue cultures; fatty-acid oxidation by beating rat heart cells; myofibrillar proteins, with a special interest in biosynthesis and degradation of cardiac myosin; the use of beating cultured rat heart cells in the study of anesthetic depression of rate and intensity of beating; and the use of heart cells in culture as an alternate model for drug testing.  McCarl was promoted to associate professor in 1969, and then named professor in 1974.  He served as Associate Dean of the Penn State Graduate School from 1982 until 1991 and was Director of Penn State's Intercollege Research Program from 1985 until 1991.  He retired with the title professor emeritus in 1991.

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McCarthy is a 5th year student conducting research in the Booker Lab under the guidance of her mentor Squire Booker, a Howard Hughes Medical Investigator, Eberly Distinguished Chair in Science and Evan Pugh Professor of Chemistry and Biochemistry and Molecular Biology.  Her research primarily focuses on the protein enzyme lipoyl synthase, or LipA.  LipA is a member of the radical SAM superfamily and uses radical chemistry in order to complete its reactions.  LipA makes the molecule lipolic acid which is an essential molecule for many different processes throughout the body, such as energy metabolism.  In order to do this LipA inserts sulfur atoms onto an unactivated 8 carbon chain using two 4 iron – 4 sulfur metal clusters.  Prior to McCarthy’s research it was believed that the second metal cluster (4 sulfur) was destroyed during the reaction which would render the enzyme dead as it no longer had its sulfur source to continue completing reactions.

 

McCarthy’s research focused heavily on the mechanism by which LipA is regenerated after the destruction of its second metal cluster so that it can become catalytic and continue making lipolic acid.  She identified a helper protein in the process that targets LipA called NfuA.  This helper protein, also containing an iron – sulfur cluster, essentially targets LipA and regenerates the second metal cluster used in the reaction to make lipolic acid.

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NfuA is found in E. coli, but humans have a different version, or homolog, called NFU1.  There have been many documented cases of patients with NFU1 mutations having horrible diseases caused by lipolic acid deficiencies that usually result in death.  Prior to McCarthy’s work little was known as to why these mutations in NFU1 caused these horrible diseases.  It is possible that the LipA in patients with these particular mutations do not have the ability to make enough lipolic acid, an essential molecule, with normal Nfu1 to regenerated it.

 

In a second paper currently in review by McCarthy, she seeks to ask and answer a second question which is how the mechanism that NfuA uses to target LipA works.  With the help of two undergraduate researchers in the lab, Ananda Rankin and Zerick Dill, McCarthy has created various versions of the helper protein NfuA and identified the domain, or piece of NfuA, that is responsible for recognizing and targeting LipA.  She then has taken the research one step further by taking the domain she identified and attaching it to another NfuA-like protein from a different organism that lacks this domain to observe its behavior.  She has found that by attaching the identified domain to another NfuA-like protein, the protein reacted similarly to E.coli NfuA and targeted the E. coli LipA protein.

 

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Though McCarthy has made progress in understanding how the helper protein, NfuA, targets and recognizes the protein LipA there are still several questions she seeks to understand.  For example, her research seks to answer how the sulfur is inserted into unactivated carbon atoms, how lipolic acid is synthesized in the cell, and how the iron – sulfur clusters are transported in the cell to proteins that need them for their reactions.  “The transferring of these iron – sulfur clusters in the cell is poorly understood.  Learning how these iron – sulfur clusters are assembled and then transferred to these proteins that target other specific proteins and learning how they know they need these clusters and where to go is fundamental to understand,” said McCarthy.

 

McCarthy’s research has many implications and may shed light on how other enzymes are catalytic even after they destroy themselves in their chemical reactions.  “Since we have researched LipA in detail, have good methods to study LipA and now know the target protein (NfuA), I believe our research provides a unique opportunity to study that process in greater depth,” said McCarthy.

 

McCarthy is very happy to have been named the 2018 recipient of the Richard L. and Norma L. McCarl Scholarship saying “sometimes I get so caught up and focused on my research that it doesn’t really sink in.  So, it is nice to be recognized.”  She also credits much of her success to her mentor Dr. Squire Booker referring to him as an unbelievable mentor and huge part of all of her research.  “I couldn’t imagine having a better Ph.D experience!  Between the BMMB Program, my advisor, and the opportunity to do the project that I am working on, I don’t thing I realized starting out what the next 5 years of my life would be like,” said McCarthy.  She also credits the work and support from the two undergraduate researchers working with her Ananda Rankin, a junior at Penn State & Zerick Dill, a student from Albion College who is part of the Howard Hughes Medical Institute Exceptional Research Opportunities Program.