Lecture Summaries | To Divide or Not To Divide: Control of Cell Cycle and Growth by Extracellular Cues | Biology

Lecture summaries.
WEEK #	TOPICS	LECTURE SUMMARIES
1	Introduction	Both the students and the instructors will introduce ourselves and describe our backgrounds and interests. We will discuss the class format and schedule. We will discuss the parts of a scientific article, and we will outline the basic biological topics that will be covered in the class.
2	Regulation of cell growth by the composition of its environment	When cells are presented with proper growth conditions they multiply. The better the conditions, the faster the cells grow and the larger they are. This response is virtually universal for almost all types of proliferating cells. We will discuss two papers that, under different conditions, measure various aspects of growth (the increase in cell size) and proliferation (the increase in cell number) of the model organism budding yeast and of mammalian cells. This session will focus on some of the fundamental cell physiology that we will discuss throughout the course, and will emphasize the similarities in the responses of single-cell and multicellular organisms to environmental cues. The Johnston at al. paper quantitatively shows that the quality of nutrients available affects the size and growth rate of yeast cells. The Zetterberg et al. paper shows that the growth rate and cells size of mammalian cells are modulated by growth factors.
3	Identification and functional analysis of cell cycle components	When the conditions are permissive for cells to multiply, they enter a proliferative program called the cell cycle, which governs the duplication and proper segregation of the genomic material to the descendent cells. The identification of the genes responsible for the cell cycle program has been a major step in understanding of the biology of cells. Indeed, it is now well established that modulation of the function of cell cycle genes is a major mechanism of coupling cell proliferation to environmental cues. The first paper that we will discuss reports the seminal discovery of cyclins (Evans et al.), proteins that drive the transitions of cell cycle processes in eukaryotic cells. The second paper orders the time of function of proteins required for cell cycle completion in budding yeast (Hartwell).
4	Bacterial differentiation in response to starvation and cell signaling	Bacteria proliferate in the presence of nutrients or enter specialized, protective and adaptive cell division programs when starved. The commitment to these specialized divisions is regulated not only by the availability of nutrients but also by the concentration of the bacterial cells in the environment. The ability of bacteria to signal each other and sense (count) themselves is widely conserved, although different species use different methods of signaling. We will discuss a paper that demonstrated that for the soil bacterium Bacillus subtilis, commitment to the specialized and protective cell division (sporulation) requires not only nutrient deprivation but also cell signaling (Grossman and Losick). The second paper describes how bacteria assemble the machinery to take in exogenous DNA when starved, a process that is also regulated by cell signaling (Hahn et al.).
5	Lab Visit	Lab Visit. We will visit the Amon lab at MIT. We will measure the sizes of yeast cells and look at their proliferation state and ability to differentiate. Samples will be prepared ahead of time, and the students will help with the analysis of the results and the interpretations. We will also observe techniques discussed during in class. Alternatively, if the students prefer, we could all attend the MIT Biology colloquium seminar on Dec 4^th by Joanna Wysocka on the subject of "Epigenetic Regulation of Differentiation and Development."
6	Genetic regulation of cell fate decision-making in yeast	During starvation, diploid yeast cells can enter the G0 state, also known as the quiescent state, or they can progress to enter a gametic program, called sporulation. Cells that enter the sporulation program undergo a specialized and highly conserved cell cycle meiosis, the end products of which are four haploid gametes (spores). The decision to enter this key developmental process depends on environmental factors as well as genetic components. We will discuss how genetic variation as well as ploidy play important roles in controlling entry into a G0 state or into sporulation. First, we will read a paper that identified genetic differences that affected the propensity of two different yeast strains to sporulate (Deutschbauer and Davis). The second paper elucidates the mechanism of how diploid, but not haploid, cells can enter the sporulation program (Hongay et al.).
7	Growth and proliferation promoting pathways I: Ras	Signaling cascades that are evolutionarily conserved among eukaryotes regulate the capacity of cells to make proteins and grow in the presence of nutrients. These signaling pathways sense the availability and quality of nutrients and modulate ribosome assembly, translation, cell cycle commitment, and gene expression. We will discuss pathways that regulate growth in two sessions. In this session we will discuss the Ras pathway in different organisms. Ras induces growth in the presence of glucose in yeast, and in response to growth factors in multicellular organisms. The first paper that we will discuss identifies a major regulator of Ras in yeast, Cdc25, and shows how Ras is regulated by Cdc25 in response to nutrients (Broek et al.). The second paper describes a clever genetic screen that implicated the Ras signaling pathway in the development of Drosophila photoreceptor cells (Simon et al).
8	Growth and proliferation promoting pathways II: TOR	We will continue the discussion of growth-regulating pathways by introducing two papers describing the TOR (Target Of Rapamycin) complex and its regulation. TOR has a role similar to that of Ras, and the two complexes affect the function of many of the same proteins; however, what they sense and how seem very distinct. TOR is sensitive to nitrogen source and amino acid availability, as well as to some mechanical stimuli, although how TOR senses each is still not clear. We will discuss how the composition of the TOR complexes was determined in yeast (Loewith et al.), as well as new evidence concerning how TOR is regulated by its cellular localization in mammalian cells (Korolchuk et al.).
9	Nutrient control of entry into sporulation	The signals required for yeast cells to enter sporulation are multiple. In addition to genetic determinants that were discussed in week 5, entry into sporulation requires several starvation signals. The inactivation of the two molecular pathways RAS and TOR (see weeks 7 and 8) are key to triggering entry into sporulation. These starvation signals converge on the promoter of a master regulator of entry into sporulation. First, we will discuss a paper that identified RAS as a major pathway controlling entry into sporulation in yeast (Matsumoto et al.). Second, we will discuss a paper that analyzed how the starvation signals converge to the promoter of the yeast master regulator of entry into sporulation, IME1 (Sagee et al.).
10	Biofilm formation by yeast and bacteria	Formation of surface-associated communities of cells, also known as biofilms, functions as a cellular survival strategy and also plays key roles in human disease. The formation of a biofilm might be the underlying process of how single-celled organisms evolved to become multicellular. Biofilm formation is controlled by intrinsic cellular communication and environmental factors. This week we will discuss how multicellularity/biofilm formation is regulated in bacteria and yeast. First we will discuss a paper that describes a quorum sensing mechanism for triggering multi-cellularity of Bacillus subtilis (Lopez et al.). Second, we will discuss how a single gene induces biofilm-like behavior in budding yeast and how this increases tolerance to environmental stress (Smukalla et al.).
11	Repression of gene transcription in the absence of environmental stimuli	For cells to adjust to environmental changes, a tight and well regulated signaling and transcription program is required. Aberrant expression of genes can be fatal to a cell's survival or to development of higher eukaryotes. To ensure that environmental signals and gene expression are appropriately coordinated, gene expression is regulated by a myriad of protein complexes, including transcription factors, chromatin remodellers, and the RNA polymerase II machinery. This week we will discuss mechanisms that insure that genes are expressed only at the right time. First, we will consider a paper that identified mutations that causes genes to be expressed even when they need to be turned off (Prelich and Winston). The second paper discusses how the activation of transcription involving nuclear hormone receptors is tightly regulated by the chromatin state in mammalian cells (Garcia-Bassets et al.).
12	Environmental control of cellular lifespan	Throughout this course we have discussed how cells sense the environment and how this sensing affects cell physiology. This week we will discuss how the environment regulates the lifespan of cells. The lifespan of eukaryotic cells as well as whole organisms is limited and controlled by intrinsic and environmental factors. For example, yeast cells exposed to a so-called "calorie restricted environment" have a longer lifespan compared to cells grown in a nutrient-rich environment. In recent years many signaling pathways involved in controlling lifespan have been identified. We will consider two of these pathways. First, we will discuss how calorie restriction extends lifespan by increasing respiration (Lin et al.). Second, we will discuss how certain chromatin modifications affect cellular lifespan (Dang et al.).
13	Part 1: Germ cell differentiation in mammals	Germ cells are critical for sexual reproduction. The timing of entry in the meiosis program determines how germ cells develop into oocytes or sperm. Although the establishment of germ cells happens very early in development, the signals that trigger entry into meiosis are generally much later. This week we will discuss the external and internal signals required for mammalian germ cells to enter meiosis. The first paper discusses how retinoic acid induces meiosis in germ cells of the fetal gonad (Lin et al.).
	Part 2: Growth pathways in disease and development	Proper regulation and functioning of growth-promoting pathways is essential for organ development in multicellular organisms. Misregulation of these pathways often leads to disease states or death. For example, mutations in genes regulating cell proliferation and growth are ubiquitous in tumors. We will discuss a paper that describes the isolation and identification of Ras as an oncogene (a tumor-promoting gene) from cancer cells (McCoy et al.).
14	Final Oral Presentations	We will have the presentations of the final assignment, and we will discuss the how the course went, including filling out the course evaluation forms.