BBio 351 – October 6, 2015 Outline for today (will spill into next lecture): 1.Kayser et al. 2014, continued 2.Homeostasis (Sherwood ) Homeostasis Negative feedback Variations: feedforward control, positive feedback 3.Cell signaling (Sherwood 3.5) Intercellular signaling Intracellular signaling (signal transduction)

Survey results as of Sunday afternoon Other courses right now? BCHEM 237 (Organic Chemistry 1) = 13 BBIO 360 (Genetics) = 10 BBIO 380 (Cell Biology) = 9 etc. Future plans Medical school = 20 Physical Therapy school = 6 Dental school = 5 etc.

Back to Kayser et al Overview: figure titles collectively summarize the paper fairly well! Fig. 1: Reduced arousal and increased resistance to sleep deprivation in young flies Fig. 2: Reduced dopamine signaling underlies ontogenetic sleep changes Fig. 3: Hypoactivity of dFSB-projecting dopaminergic neurons in young flies Fig. 4: The sleep-promoting dFSB is more active in young flies Fig. 5: Sleep in young flies is required for courtship behaviors and circuitry development

Kayser et al. 2014: background Overview of fly central nervous system animals.io9.com/see-the-inside-of-a-fruit-fly-brain

Kayser et al. 2014: background Genetics concepts and tools: Promoter vs. coding region Reporter gene Transcriptional fusion vs. translational fusion

Kayser et al. 2014: background jeb.biologists.org/content/210/9/1632/F1.large.jpg Example of a genetic tool: the GAL4-UAS system Other tools: CREB-Luciferase CaLexA DopR-Tango

Kayser et al. 2014: genetic notation TH-GAL4>UAS-dTrypA??? UAS-mCD8::GFP???

How dopamine is made Figure from Principles of Human Physiology by Cindy L. Stanfield

Fig. S10. Model for dopaminergic developmental program underlying sleep ontogeny. (A) In mature adults, distinct populations of dopaminergic neurons contribute parallel sleep-wake pathways, some via dFSB. Separate MB signals also drive sleep. TH+ neurons also project to MB (gray), though not in a known sleep-relevant manner. (B) In young flies, dFSB-projecting TH neurons are less active, leading to increased dFSB activity and excess sleep.

Discussion section of Kayser et al. “Sudden infant death syndrome usually occurs early in infant life, and (along with environmental factors) abnormalities in sleep structure are arousal are thought to play a significant role (40, 41). We suggest that the dysfunction of specific molecular signals or circuits could underlie pathological sleep/wake imbalances during mammalian development.” “Many neuropsychiatric diseases are increasingly viewed as synaptic and developmental in origin (54), and sleep abnormalities are pervasive in psychiatric illness (55). Sleep during critical periods of development may therefore play an important role in diseases that manifest later in life.”

Main take-aways from Kayser et al.?

Homework Due by start of your lab section download or print lab paragraph on animals (Canvas) Due at start of next lecture (10/8) write one quiz question about Kayser et al., along with your answer (Canvas) download or print slides for 10/8 (to be posted by 10/7 at noon) and skim corresponding textbook pages

Homeostasis and its variations (Sherwood ) Meaning of “homeostasis”? What physiological variables are kept in homeostasis? How?

Negative feedback S. Freeman et al., Biological Science

Graphing a regulated variable over time Time

Negative feedback: the concept of gain

Is gain altered in type 2 diabetes mellitus? [insulin] in blood Rate of glucose removal from blood Function of insulin =

Can the gain ever be too high?

Variations on negative feedback: positive feedback Sherwood Fig. 1-10b

Variations on negative feedback: feedforward control Sherwood Fig. 1-9b

Control of muscle glycolysis? Feedback hypothesis Buildup of ATP breakdown products stimulate glycolytic ATP production Feedforward hypothesis Muscle contraction signal stimulates glycolytic ATP production in anticipation of need for more ATP

Control of muscle glycolysis? K.E. Conley et al., Journal of Physiology 1998

Cell signaling Intercellular signaling Intracellular signaling (signal transduction) Connection with negative feedback?

Intercellular signaling F. Martini et al., Fundamentals of Anatomy & Physiology (simpler version of Sherwood Fig. 3-16)

Structural classes of signal molecules 3 main groups ShutterStock.com; Wikimedia; Wikipedia

Relative size Hydrophobic? Hydrophilic? Location of receptors (Cell surface? Interior?)

Components of signal transduction Tyrosine kinase receptors G proteins Cyclic nucleotides (cAMP, cGMP) Calcium (Ca 2+ ) Transcription factors

Signal transduction: tyrosine kinase receptors Sherwood Fig. 3-18

Signal transduction: G proteins Sherwood Fig. 3-17c

Signal transduction: cyclic nucleotides Sherwood Fig. 3-19

Signal transduction: calcium Sherwood Fig. 3-20

Signal transduction: transcription factors

Example of signal transduction: phototransduction in photoreceptors of retina upload.wikimedia.org/wikipedia/commons/d/de/Phototransduction.png

Amplification of signal Sherwood Fig. 3-21

Disadvantages of amplification?