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Course Work
Receptive audience
In Endocrinology I Matthew Brady introduces cell signaling’s core concept: every hormone needs a receptor.
It’s Monday, the first morning of fall quarter, and students filter into room 205, a small lecture hall in the Biological Sciences Learning Center. The room is cacophonous as the undergraduates catch up after summer break. One complains about the grade she received last year in Developmental Biology, another about the lack of air conditioning in her previous class. “There are two handouts by the door,” Matthew Brady, AB’87, PhD’94, shouts above the din, echoing a handwritten instruction on the board.
By 11:30 there are about 30 students—half of them men, half women—waiting for BIOS 25266 Endocrinology I: Cell Signaling to begin. Sitting at the back of the class are Clive Palfrey, professor of neurobiology and the course’s codirector, and Michael Roe, assistant professor of endocrinology and one of the course’s four instructors.
Brady, winner of a 2007 Quantrell award for undergraduate teaching, begins with the usual first-day overview. After introducing Palfrey, Roe, and teaching assistant Arpad Danos, AB’01, it’s on to grades, online lecture notes—students are strongly recommended to review these before coming to class—and the lack of a textbook. “E-mail is the best way to get hold of me. If I do not respond in 24 hours,” Brady continues, “I did not get your e-mail.”
Housekeeping details finished, Brady warns, “Eyes up, no peeking.” The answer to the question he’s about to ask is on the first page of one of the day’s handouts, a hard copy of his lecture slides: “What are the four most fundamental drives humans have?”
Responses come quickly from different parts of the room: Hunger. Sleep. “Sex,” says a male student in the front row; he’s wearing a red “Orientation 2005” T-shirt.
“Reproduction,” Brady rephrases. “And the final, more general one?”
“Survival,” says the same student.
“Exactly,” says Brady. “I would argue that these four primal urges are the fundamental basis of endocrinology. Endocrinology plays a key role in meeting and overcoming each of these urges.”
Brady’s first slide is very simple, showing the four words connected by two-way arrows, forming a rectangle around the word brain. “Actually, complete sleep deprivation will kill you faster than complete food deprivation,” Brady observes. “Now, which is the most important organ in the body?”
It’s a quick question followed by an oddly long pause before someone finally says, “Brain.”
“Brain,” Brady repeats. “If you’re using it, yep.” The students laugh.
After a slide showing a close-up of a leaf and a long view of a forest (to remind students not to lose the big picture as he gets into the more technical material) comes a slide titled “Cell Signaling Paradigms.”
“This is a key point in all of cell signaling,” Brady says, with emphasis: “if…that…cell…type…does…not…have…a…receptor, it will never see the signal.”
He flips to a different slide with the same title. “In endocrinology—,” he begins, then interrupts himself: “Can anybody tell me the difference between an endocrine cell and an exocrine cell? Any classics majors here? What’s the difference between endo and exo?”
“Inside, outside.” It’s the front-row student again.
Brady nods, then explains that exocrine glands—sweat glands, for example—excrete substances to the outside of the body. In contrast, endocrine glands secrete hormones on the inside: that is, into the bloodstream. These hormones circulate all over the body before they finally find their target cells and are able to signal. “And if the cell doesn’t have a receptor,” Brady repeats, “it doesn’t matter how much hormone is out there. It’s never going to see it, it’s never going to respond to it.”
Brady’s slides are peppered with bullet points, abbreviations, and arrows pointing this way and that. Some of the abbreviations are defined on the slides, such as G-Protein coupled receptors (GPCRs), while others remain mysterious, at least for today: Ach, GABA, CNTF, RANTES. “This is just a general overview class, so don’t sweat the details,” Brady reassures his students.
He comes to a slide titled “Protein phosphorylation,” a concept he calls “deceptively simple but really important.” Brady simplifies the concept even further with a quick diagram on the board, using the ubiquitous arrows to show how a protein in state A can turn into state B and vice versa. “At equilibrium, the forward reaction”—he gestures, showing how A converts to B—“is balanced by the reverse reaction,” B turning into A.
To change the amount of B, he says, “you can either change the forward rate, the reverse rate, or both. It’s really important to keep this reverse reaction in mind—too often we just think forward.”
Brady sketches out another example, “a little more complicated.” It’s blood glucose, his area of research. (After earning his PhD in pharmacological and physiological sciences, Brady was a researcher at Parke Davis, a pharmaceutical company, for six years.) “You want to maintain your blood glucose at five millimolar,” or five millimoles of glucose per liter of blood, he says. “What is the hormone that reduces blood glucose?”
“Insulin,” the class responds like a congregation sure of its catechism.
Underneath “insulin” he writes “glucagon,” one of several hormones that increase blood glucose. “Two opposing hormones, working together to maintain blood glucose at five millimolar,” he explains. “So if you wanted to raise blood glucose, you could drop the level of insulin, you could increase the level of glucagon, or you could do both. What’s one other thing you could do?”
“Eat candy,” says the front-row student.
Brady nods: “You could increase the input.”
Brady moves back to the lectern. The students flip through their printouts, occasionally scribbling notes on the blank lines provided. Time is running short; Brady skips a slide.
The lecture nearly over, Brady quickly covers cell signaling, disease, and drug therapy. In chronic myelogenous leukemia (a rare form of cancer that affects about 20,000 people in the U.S.) parts of chromosomes 9 and 22 get mixed up, he explains. “This freaky kinase,” an enzyme involved in cell signaling, “doesn’t exist in any other cell, only in the cancerous cells. “So right away, that’s an attractive drug target.” Ideally a drug would affect only the disease tissue and not the rest of the body.
A “really nice paper” on Chalk, the University’s online site for course materials, explains how a new drug was developed for this disease, Brady says, detailing the signaling pathway, the design of the drug, the clinical trials. The drug blocks the binding of adenosine triphosphate (ATP), the molecule that carries energy to every single cell in the body. “Anybody think why an ATP–binding inhibitor might not be a great target in general?”
“It might be irreversible,” offers the guy in the front row.
“Might be,” says Brady, clearly looking for a dif\-ferent answer. He re-phrases the question: “Again, what’s the biggest factor with drug targets?”
The class remains silent. Near the back, a young woman in a strappy hot-pink sundress and high-heeled black wedges whispers under her breath: “Specificity.”
It’s much too quiet for Brady to hear. “Specificity,” he says.
Brady’s last slide is a recap of his initial introduction: “Just to close,” he says, “again, I’m Matthew Brady, Clive Palfrey is the course codirector, Arpad is the TA. We’re here to help. Please get in touch with us as soon as possible if you need anything.” In addition to these three names, the slide has two images: a large, acronym-packed diagram of cell signaling and a small still of Dr. Evil from the Austin Powers movies. Dr. Evil holds his pinkie to his lips in his trademark pose. What he’s signaling is up to the students to figure out.
By 11:30 there are about 30 students—half of them men, half women—waiting for BIOS 25266 Endocrinology I: Cell Signaling to begin. Sitting at the back of the class are Clive Palfrey, professor of neurobiology and the course’s codirector, and Michael Roe, assistant professor of endocrinology and one of the course’s four instructors.
Brady, winner of a 2007 Quantrell award for undergraduate teaching, begins with the usual first-day overview. After introducing Palfrey, Roe, and teaching assistant Arpad Danos, AB’01, it’s on to grades, online lecture notes—students are strongly recommended to review these before coming to class—and the lack of a textbook. “E-mail is the best way to get hold of me. If I do not respond in 24 hours,” Brady continues, “I did not get your e-mail.”
Housekeeping details finished, Brady warns, “Eyes up, no peeking.” The answer to the question he’s about to ask is on the first page of one of the day’s handouts, a hard copy of his lecture slides: “What are the four most fundamental drives humans have?”
Responses come quickly from different parts of the room: Hunger. Sleep. “Sex,” says a male student in the front row; he’s wearing a red “Orientation 2005” T-shirt.
“Reproduction,” Brady rephrases. “And the final, more general one?”
“Survival,” says the same student.
“Exactly,” says Brady. “I would argue that these four primal urges are the fundamental basis of endocrinology. Endocrinology plays a key role in meeting and overcoming each of these urges.”
Brady’s first slide is very simple, showing the four words connected by two-way arrows, forming a rectangle around the word brain. “Actually, complete sleep deprivation will kill you faster than complete food deprivation,” Brady observes. “Now, which is the most important organ in the body?”
It’s a quick question followed by an oddly long pause before someone finally says, “Brain.”
“Brain,” Brady repeats. “If you’re using it, yep.” The students laugh.
After a slide showing a close-up of a leaf and a long view of a forest (to remind students not to lose the big picture as he gets into the more technical material) comes a slide titled “Cell Signaling Paradigms.”
“This is a key point in all of cell signaling,” Brady says, with emphasis: “if…that…cell…type…does…not…have…a…receptor, it will never see the signal.”
He flips to a different slide with the same title. “In endocrinology—,” he begins, then interrupts himself: “Can anybody tell me the difference between an endocrine cell and an exocrine cell? Any classics majors here? What’s the difference between endo and exo?”
“Inside, outside.” It’s the front-row student again.
Brady nods, then explains that exocrine glands—sweat glands, for example—excrete substances to the outside of the body. In contrast, endocrine glands secrete hormones on the inside: that is, into the bloodstream. These hormones circulate all over the body before they finally find their target cells and are able to signal. “And if the cell doesn’t have a receptor,” Brady repeats, “it doesn’t matter how much hormone is out there. It’s never going to see it, it’s never going to respond to it.”
Brady’s slides are peppered with bullet points, abbreviations, and arrows pointing this way and that. Some of the abbreviations are defined on the slides, such as G-Protein coupled receptors (GPCRs), while others remain mysterious, at least for today: Ach, GABA, CNTF, RANTES. “This is just a general overview class, so don’t sweat the details,” Brady reassures his students.
He comes to a slide titled “Protein phosphorylation,” a concept he calls “deceptively simple but really important.” Brady simplifies the concept even further with a quick diagram on the board, using the ubiquitous arrows to show how a protein in state A can turn into state B and vice versa. “At equilibrium, the forward reaction”—he gestures, showing how A converts to B—“is balanced by the reverse reaction,” B turning into A.
To change the amount of B, he says, “you can either change the forward rate, the reverse rate, or both. It’s really important to keep this reverse reaction in mind—too often we just think forward.”
Brady sketches out another example, “a little more complicated.” It’s blood glucose, his area of research. (After earning his PhD in pharmacological and physiological sciences, Brady was a researcher at Parke Davis, a pharmaceutical company, for six years.) “You want to maintain your blood glucose at five millimolar,” or five millimoles of glucose per liter of blood, he says. “What is the hormone that reduces blood glucose?”
“Insulin,” the class responds like a congregation sure of its catechism.
Underneath “insulin” he writes “glucagon,” one of several hormones that increase blood glucose. “Two opposing hormones, working together to maintain blood glucose at five millimolar,” he explains. “So if you wanted to raise blood glucose, you could drop the level of insulin, you could increase the level of glucagon, or you could do both. What’s one other thing you could do?”
“Eat candy,” says the front-row student.
Brady nods: “You could increase the input.”
Brady moves back to the lectern. The students flip through their printouts, occasionally scribbling notes on the blank lines provided. Time is running short; Brady skips a slide.
The lecture nearly over, Brady quickly covers cell signaling, disease, and drug therapy. In chronic myelogenous leukemia (a rare form of cancer that affects about 20,000 people in the U.S.) parts of chromosomes 9 and 22 get mixed up, he explains. “This freaky kinase,” an enzyme involved in cell signaling, “doesn’t exist in any other cell, only in the cancerous cells. “So right away, that’s an attractive drug target.” Ideally a drug would affect only the disease tissue and not the rest of the body.
A “really nice paper” on Chalk, the University’s online site for course materials, explains how a new drug was developed for this disease, Brady says, detailing the signaling pathway, the design of the drug, the clinical trials. The drug blocks the binding of adenosine triphosphate (ATP), the molecule that carries energy to every single cell in the body. “Anybody think why an ATP–binding inhibitor might not be a great target in general?”
“It might be irreversible,” offers the guy in the front row.
“Might be,” says Brady, clearly looking for a dif\-ferent answer. He re-phrases the question: “Again, what’s the biggest factor with drug targets?”
The class remains silent. Near the back, a young woman in a strappy hot-pink sundress and high-heeled black wedges whispers under her breath: “Specificity.”
It’s much too quiet for Brady to hear. “Specificity,” he says.
Brady’s last slide is a recap of his initial introduction: “Just to close,” he says, “again, I’m Matthew Brady, Clive Palfrey is the course codirector, Arpad is the TA. We’re here to help. Please get in touch with us as soon as possible if you need anything.” In addition to these three names, the slide has two images: a large, acronym-packed diagram of cell signaling and a small still of Dr. Evil from the Austin Powers movies. Dr. Evil holds his pinkie to his lips in his trademark pose. What he’s signaling is up to the students to figure out.
Endocrinology I grew out of a course called Cell Signaling, designed and taught by Clive Palfrey. (After earning his AB at Chicago, Brady worked for a year in Palfrey’s lab; Palfrey later supervised Brady’s thesis.) The course is now part of a three-quarter sequence that includes Endocrinology II: Systems and Physiology, and Endocrinology III: Human Disease. Biological Sciences majors who complete all three courses earn a specialization in Endocrinology.
Endocrinology I has no required textbook. “Cell signaling is a quickly evolving field,” says Brady. “It’s very difficult to come up with a textbook that’s both up to date and accessible.” A recommended textbook, Signal Transduction by Bastien D. Gomperts et al (2003), is on reserve at Crerar, but the lecture notes should be sufficient to do well in the course, Brady says.
Grades are based primarily on a midterm (30 percent) and a final (50 percent), which is not cumulative, so students can concentrate on the concepts in the second half of the quarter. There are also four homework assignments (5 percent each). “Several people on the evaluations last year asked for more homework assignments. I know this is U of C,” Brady teases his students, “but come on now.” Nonetheless, he’s posted last year’s assignments on Chalk “in case you have a social life cropping up.”
